理学博士, 名古屋大学, Mar. 1979

Ph. D, Nagoya University

Bioluminescence

Natural Products

Biological Organic Chemistry

生物発光

天然有機化合物

生物有機化学

Life sciences, Bioorganic chemistry

Nanotechnology/Materials, Biochemistry

Nanotechnology/Materials, Molecular biochemistry

Apr. 2019 - Present
The University of Electro-communications, Center of Neuroscinece and Biomedical Engineering, Visiting Professor

Apr. 2013 - Present
The University of Electro-Communications, 名誉教授

Apr. 2013 - Mar. 2019
The University of Electro-communications, Brain Science Inspired Life Support Research Center, Designated Professor of Bio-Organic Chemistry

Apr. 2010 - Mar. 2013
The University of Electro-communications, Graduate School of Informatics and Engineering, Professor

Apr. 1994 - Mar. 2010
The University of Electro-communications, Faculty of Electro-communications, Professor

Mar. 1984 - Mar. 1994
Nagoya University, Faculty of Science, Associate Professor

Jun. 1980 - Mar. 1984
Nagoya University, Faculty of Science, Assistant Professor

Apr. 1973 - Jun. 1980
Ono Pharmaceutical Co. Ltd., Central Reasearch Lab, Researcher

Apr. 1971 - Mar. 1973
Nagoya University, Graduate School, Division of Natural Science, Department of Chemistry

Apr. 1966 - Mar. 1971
Nagoya University, Faculty of Science, Department of Chemistry

2001 - 2003
Assocate editor of Bull. Chem. Soc. Jpn., The Chemical Society of Japan, Society

2001 - 2003
欧文誌編集委員, 日本化学会, Society

1988 - 1988
Assocate editor of Bull. Chem. Soc. Jpn., The Chemical Society of Japan, Society

1988 - 1988
欧文誌編集委員, 日本化学会, Society

Feb. 1987
Incentive Award in Synthetic Organic Chemistry, Japan (The Society of Synthetic Organic Chemistry, Japan)

Toward bioluminescence in the near-infrared region: Tuning the emission wavelength of firefly luciferin analogues by allyl substitution
Nobuo Kitada; Tsuyoshi Saitoh; Yuma Ikeda; Satoshi Iwano; Rika Obata; Haruki Niwa; Takashi Hirano; Atsushi Miyawaki; Koji Suzuki; Shigeru Nishiyama; Shojiro A. Maki
Tetrahedron Letters, Elsevier Ltd, 59, 12, 1087-1090, 21 Mar. 2018, Peer-reviwed, The synthesis and bioluminescence of allyl-substituted luciferin derivatives as substrates for firefly luciferase are reported. The allylation of luciferins induced bathochromic shift (15–40 nm) of the bioluminescence emission. Upon combination with other chemical modifications for bioluminescence wavelength tuning, novel red emitting luciferin analogues were obtained with emission maxima at 685 and 690 nm.
Scientific journal, English

Aspiration Risk Detection Using Oral Administration of Fluorescent Food --- Preliminary Experiments Using Meat Phantoms ---
Takahiro SUZUKI; Ryohei SAITO; Nobuo KITADA; Takuji KOIKE; Shojiro MAKI; Yukihiro MICHIWAKI; Goro NISHIMURA; Haruki NIWA; Yukio YAMADA
2017 IEEE International Conference on Cyborg and Bionic Systems (CBS 2017), IEEE, 1, 17 Oct. 2017, Peer-reviwed
International conference proceedings, English

A luciferin analogue generating near-infrared bioluminescence achieves highly sensitive deep-tissue imaging.
Takahiro Kuchimaru; Satoshi Iwano; Masahiro Kiyama; Shun Mitsumata; Tetsuya Kadonosono; Haruki Niwa; Shojiro Maki; Shinae Kizaka-Kondoh
Nature communications, 7, 11856-11856, 14 Jun. 2016, Peer-reviwed, True, In preclinical cancer research, bioluminescence imaging with firefly luciferase and D-luciferin has become a standard to monitor biological processes both in vitro and in vivo. However, the emission maximum (λmax) of bioluminescence produced by D-luciferin is 562 nm where light is not highly penetrable in biological tissues. This emphasizes a need for developing a red-shifted bioluminescence imaging system to improve detection sensitivity of targets in deep tissue. Here we characterize the bioluminescent properties of the newly synthesized luciferin analogue, AkaLumine-HCl. The bioluminescence produced by AkaLumine-HCl in reactions with native firefly luciferase is in the near-infrared wavelength ranges (λmax=677 nm), and yields significantly increased target-detection sensitivity from deep tissues with maximal signals attained at very low concentrations, as compared with D-luciferin and emerging synthetic luciferin CycLuc1. These characteristics offer a more sensitive and accurate method for non-invasive bioluminescence imaging with native firefly luciferase in various animal models.
Scientific journal, English

Synthesis and evaluation of new firefly luciferin analogues for luminescent materials
Ioka, Shuji; Saitoh, Tsuyoshi; Iwano, Satoshi; Suzuki, Koji; Maki, Shojiro; Niwa, Haruki; Miyawaki, Atsushi; Imoto, Masaya; Nishiyama, Shigeru
Chemistry, A European Journal, Chemistry, A European Journal, 22, 1-9, 2016, Peer-reviwed, ホタル生物発光基質のチアゾリン環（右環部）の硫黄原子を炭素原子に変換した新規化合物の合成と発光活性およびその活性についてまとめた．
Scientific journal, English

"Synthesis and evaluation of the luminescent properties of firefly luciferin analogues "
Ioka, Shuji; Saitoh, Tsuyoshi; Iwano, Satoshi; Suzuki, Koji; Maki, Shojiro; Niwa, Haruki; Miyawaki, Atsushi; Imoto, Masaya; Nishiyama, Shigeru
Chemistry, A European Journal, 22, 1-9, 2016, Peer-reviwed, ホタル生物発光基質のチアゾリン環（右環部）の硫黄原子を炭素原子に変換した新規化合物の合成と発光活性およびその活性についてまとめた．
Scientific journal, English

Spectroscopic properties of BF2 complexes of N-(5-phenyl-2- pyrazinyl)pivalamides exhibiting fluorescence in solution and solid state (http://dx.doi.org/10.1016/j.jphotochem.2015.10.014)
Sojiro Hachiya; Daisuke Hashizume; Hiroshi Ikeda; Minoru Yamaji; Shojiro Maki; Haruki Niwa; Takashi Hirano
Journal of Photochemistry and Photobiology A: Chemistry, 331, 206-214, 2016, Peer-reviwed, Boron difluoride (BF2) complexes of N-(5-phenyl-2-pyrazinyl)pivalamide and its derivatives having a substituent on the phenyl group were prepared and their spectroscopic properties were investigated. It was found that the BF2 complexes show fluorescence in solution and the solid state. The origins of the fluorescence properties are discussed on the basis of the fluorescence yields and lifetimes, crystal structures and DFT calculations. The present work would provide a guide to design BF2 complexes of amidopyrazines exhibiting solid state fluorescence.
Scientific journal, English

Multicolor Bioluminescence Obtained Using Firefly Luciferin
Masahiro Kiyama; Ryohei Saito; Satoshi Iwano; Rika Obata; Haruki Niwa; Shojiro A. Maki
CURRENT TOPICS IN MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBL LTD, 16, 24, 2648-2655, 2016, Peer-reviwed, Firefly bioluminescence is widely used in life science research as a useful analysis tool. For example, the adenosine-5'-triphosphate (ATP)-dependent enzymatic firefly bioluminescence reaction has long been utilized as a microbial monitoring tool. Rapid and sensitive firefly luciferin-luciferase combinations are used not only to measure cell viability but also for reporter-gene assays. Recently, bioluminescence was utilized as a noninvasive, real-time imaging tool for living subjects to monitor cells and biological events. However, the number of commercialized luciferase genes is limited and tissue-permeable near-infrared (NIR) region emitting light is required for in vivo imaging. In this review, recent studies describing synthetic luciferin analogues predicted to have red-shifted bioluminescence are summarized. Luciferase substrates emitting red, green, and blue light that were designed and developed in our laboratory are presented. The longest emission wavelength of the synthesized luciferin analogues was recorded at 675 nm, which is within the NIR region. This compound is now commercially available as "Aka Lumine (R)".
Scientific journal, English

Fluorescence Properties of Diphenylthiazolo[4,5-b]pyrazines Tuned by Donor-Acceptor Substituent Effects
Tatsuki Nakagawa; Minoru Yamaji; Shojiro Maki; Haruki Niwa; Takashi Hirano
PHOTOCHEMISTRY AND PHOTOBIOLOGY, WILEY-BLACKWELL, 91, 4, 807-813, Jul. 2015, Peer-reviwed, Fluorescence properties of 2,6- and 2,5-diphenylthiazolo[4,5-b]pyrazine (TPy) derivatives having an electron-donating substituent (methoxy and dimethylamino) on the 6- and 5-phenyl groups were studied. It was found that 2,6-diphenyl derivatives fluoresce more efficiently than 2,5-diphenyl derivatives. Furthermore, a 2,6-diphenyl derivative having an additional cyano group on the 2-phenyl ring was an excellent fluorophore showing a wide solvatochromism with great fluorescence yields. Based on the obtained spectroscopic data and mechanistic explanations concerning the substituent effects on the fluorescence properties, useful information on designing new TPy fluorophores is provided.
Scientific journal, English

Synthesis and chemiluminescent properties of 6,8-diaryl-2-methylimidazo[1,2-alpha]pyrazin-3(7H)-ones: Systematic investigation of substituent effect at para-position of phenyl group at 8-position
Ryota Saito; Takashi Hirano; Shojiro Maki; Haruki Niwa
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY, ELSEVIER SCIENCE SA, 293, 12-25, Nov. 2014, Peer-reviwed, 6,8-Diphenylimidazopyrazinone derivatives having a substituent R (R=CF3, H, and OMe) at pare position of the 8-phenyl group were synthesized and their chemiluminescent properties were investigated. The chemiluminescence maxima (CLmax) of these compounds were observed to be in the range of 513-553 nm with a bathochromic shift that increased with the electron-withdrawing character of R, contrary to the previously observed substituent effect at the 6-postion. The chemiluminescence efficiencies (phi(CL)) of these imidazopyrazinones were improved by the introduction of a p-substituted phenyl group at the 8-position. The quantitative investigation of the three quantum efficiencies (phi(R), phi(S), and phi(FL)) whose product gives us phi(CL) revealed that the phi(CL) gains made were largely because of the increase in the values of the fluorescence quantum yields of the corresponding light emitters (phi(FL)). The yields of the singlet-excited emitters (phi(S)) during the chemiluminescent reaction were found to be very small (0.015-0.019), suggesting that one cannot construct an efficient imidazopyrazinone-chemiluminescence system that is comparable to the aequorin bioluminescence system only by using the electronic effects of substituents. (C) 2014 Elsevier B.V. All rights reserved.
Scientific journal, English

Substituent effects on fluorescence properties of thiazolo[4,5-b]pyrazine derivatives
Tatsuki Nakagawa; Minoru Yamaji; Shojiro Maki; Haruki Niwa; Takashi Hirano
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, ROYAL SOC CHEMISTRY, 13, 12, 1765-1772, 2014, Peer-reviwed, Based on spectroscopic measurements and DFT calculations, fluorescence properties of thiazolo[4,5-b]-pyrazine (TPy) derivatives with the phenyl group at the C2 position were studied. TPys were readily prepared from the corresponding amidopyrazines, which have a similar fluorescent core to a bioluminescence light emitter, Cypridina oxyluciferin. It was found that the introduction of electron-donating (methoxy and dimethylamino) groups onto the 2-phenyl moiety of the TPy derivatives, as well as the phenyl and 4-(dimethylamino) phenyl groups at C2 and C6, respectively, increases the fluorescence yield and appearance of solvatochromic character. The mechanism of increasing the fluorescence yield depending on the substituents is discussed. These findings provide useful information on designing new TPy fluorophores.
Scientific journal, English

Synthesis and luminescence properties of biphenyl-type firefly luciferin analogs with a new, near-infrared light-emitting bioluminophore
Chihiro Miura; Masahiro Kiyama; Satoshi Iwano; Kazuto Ito; Rika Obata; Takashi Hirano; Shojiro Maki; Haruki Niwa
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 69, 46, 9726-9734, Nov. 2013, Peer-reviwed, New firefly luciferin analogs of the 4,4 '-substituted biphenyl-type were synthesized. One analog with a 4 '-dimethylamino group possessed bioluminescence activity, emitting near-infrared biological window light at 675 nm suitable for deep-site bioimaging of living animals. The chemiluminescence light-emission maximum of the corresponding methyl ester of the bioluminescence active analog was 500 nm, implying that biphenyl and thiazolinone rings in the light emitter might be placed in a coplanar conformation at the polar luciferase active site. (c) 2013 Elsevier Ltd. All rights reserved.
Scientific journal, English

Development of simple firefly luciferin analogs emitting blue, green, red, and near-infrared biological window light
Satoshi Iwano; Rika Obata; Chihiro Miura; Masahiro Kiyama; Kazutoshi Hama; Mitsuhiro Nakamura; Yoshiharu Amano; Satoshi Kojima; Takashi Hirano; Shojiro Maki; Haruki Niwa
Tetrahedron, 69, 19, 3847-3856, 13 May 2013, Peer-reviwed, Simple firefly luciferin analogs emitting blue, green, and red light were developed. The longest emission maximum was observed at 675 nm, which belongs to the NIR biological window (650-900 nm), useful for deep site bioimaging of living animals. The analogs showed a slow rise of emission intensity compared with the rapid emission of natural luciferin. The light emission of the adenylated analogs was strongly enhanced compared with those of analogs themselves.© 2013 Elsevier Ltd. All rights reserved.
Scientific journal, English

Evaluation of Bioluminescence Activity of Firefly Luciferin Nucleotide Derivatives
Satoshi IWANO; Satoshi KOJIMA; Takashi HIRANO; Shojiro MAKI; Haruki NIWA
ECS Transactions, The Electrochemical society, 50, 1-3, 2013, Peer-reviwed, 天然ホタル生物発光では，発光酵素はAMP化と酸素化反応の２つの反応に関わっている，AMPの核酸と糖の部位をいくつか変えて，発光活性を測定した．その結果，

糖部位をデオキシリボースに変換すると活性が大きく減衰すること，単環性の核酸でも活性は減衰するが，発光活性さほど失われないことがわかった．
Scientific journal, English

5-[4-(Dimethylamino)phenyl]-2-benzamidopyrazines: fluorescent dyes based on Cypridina oxyluciferin
Takashi Hirano; Tatsuki Nakagawa; Ai Kodaka; Shojiro Maki; Haruki Niwa; Minoru Yamaji
RESEARCH ON CHEMICAL INTERMEDIATES, SPRINGER, 39, 1, 233-245, Jan. 2013, Peer-reviwed, To clarify the acyl substitution effect on the fluorescent property of Cypridina oxyluciferin analogs, which have the 4-(dimethylamino)phenyl group at C5, we compared the spectroscopic properties of benzamide 1b and its 2,6-dimethylphenyl derivative 1c in various solvents with those of acetamide 1a. Similarity of the fluorescence wavelengths of 1a-c indicates that the pi-electronic conjugation in the excited singlet (S-1) state is terminated at the acyl group and that the benzamide moiety in 1b has little effect on modulating the florescence color. The similar fluorescence solvatochromism of 1a-c reveals that their S-1 states have a similar intramolecular charge transfer character. The fact that 1a-c have various fluorescence quantum yields and lifetimes depending on solvent polarity and hydrogen bonding interactions in solutions provides information about the decay processes competing with the fluorescence process in the S-1 states. Among 1a-c, benzamide 1b exhibits the most sensitive variation of the fluorescence intensity depending on the solvent used. Similarity of the fluorescence spectra of 1a-c adsorbed in NaY zeolites was also observed, which indicates that the S-1 states of 1a-c give mobile conformers in the NaY supercages. The relationship between the molecular structures of 1a-c and their spectroscopic properties will provide a guide for designing a new fluorophore based on Cypridina oxyluciferin.
Scientific journal, English

Anoikis Induction and Inhibition of Peritoneal Metastasis of Pancreatic Cancer Cells by a Nuclear Factor-kappa B Inhibitor, (-)-DHMEQ
Masanori Sato; Kazuaki Nakanishi; Sanae Haga; Masato Fujiyoshi; Motoi Baba; Kazuhiro Mino; Yimin; Haruki Niwa; Hideki Yokoo; Kazuo Umezawa; Yoshihiro Ohmiya; Toshiya Kamiyama; Satoru Todo; Akinobu Taketomi; Michitaka Ozaki
ONCOLOGY RESEARCH, COGNIZANT COMMUNICATION CORP, 21, 6, 333-343, 2013, Peer-reviwed, The transcription factor nuclear factor-kappa B (NF-kappa B) plays a crucial role in pancreatic cancer (PC) progression. NF-kappa B is also involved in resistance to anoikis, a special type of apoptosis induced when cells are detached from the extracellular matrix or other cells. Anoikis resistance is related to the metastatic abilities of tumor cells; however, little is known about anoikis induction as it relates to inhibition of PC metastasis by NF-kappa B inhibitors. Here we used a specific NF-kappa B inhibitor, (-)-dehydroxymethylepoxyquinomicin (DHMEQ), to investigate anoikis induction and peritoneal metastasis suppression following NF-kappa B inhibition. We transduced Glue, a secretory form of luciferase, into a PC cell line, AsPC-1 (AsPC-1-Gluc), for our in vivo experiments. (-)-DHMEQ induced anoikis in AsPC-1-Gluc cells as measured by cell survival assays and flow cytometry. The DNA-binding activity of p65 was enhanced immediately after cell detachment from culture dishes in ELISA assays. Some antiapoptotic proteins such as cellular inhibitor of apoptotic protein-1 were consequently upregulated on Western blots. (-)-DHMEQ prevented this increase in p65 activity and the subsequent expressions of antiapoptotic molecules. In a murine xenograft model, anoikis-resistant PC cell lines tended to metastasize to the peritoneum more than anoikis-sensitive cells, suggesting a correlation between anoikis sensitivity and peritoneal metastasis. (-)-DHMEQ successfully inhibited peritoneal metastasis of AsPC-1-Gluc cells. We monitored metastasis inhibition by ex vivo chemiluminescent detection of Glue secreted from tumor cells into murine plasma and by in vivo imaging. Our results suggest that (-)-DHMEQ inhibited peritoneal dissemination by preventing anoikis resistance of PC cells.
Scientific journal, English

Spectroscopic studies of the color modulation mechanism of firefly (beetle) bioluminescence with amino-analogs of luciferin and oxyluciferin
Hirano, T; Nagai, H; Matsuhashi, T; Hasumi, Y; Iwano, S; Ito, K; Maki, S; Niwa, H; Viviani, V. R
Photochem. Photobiol. Sci., 11, 8, 1281-1284, Aug. 2012, Peer-reviwed
Scientific journal, English

Studies on (-)ESI-MS/MS of a glycosaminoglycan disaccharide N-acetyllactosamine-6,6 '-disulfate disodium salt-Charge-localization isomers
Yoko Ohashi; Masayuki Kubota; Hiroshi Hatase; Takashi Hirano; Shojiro Maki; Haruki Niwa
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY, ELSEVIER SCIENCE BV, 312, 179-184, Feb. 2012, Peer-reviwed, We previously reported the ESI-MS/MS studies on distinguishing Gal beta 1-4GlcNAc-6,6'-disulfate disodium salt from 2'-epimer,(1) namely Gal beta 1-4ManNAc-6,6'-disulfate [1]. Here, we must emphasize first that distinction of the epimeric pair was successful using either FAB or MALDI, but most effectively done by ESI mass spectrometry. However, though totally independent of our original aim of distinguishing epimers, we later realized that there were some inaccuracies in our assignment of the fragmentation path of negative product ions. Through our intensive studies to establish the right fragmentation path, we now propose a new concept of isomers caused by the difference in the localization of a negative charge in apparently the same MS1 ion of a disaccharide dibasic acid. (C) 2011 Elsevier B.V. All rights reserved.
Scientific journal, English

Spectroscopic studies of the color modulation mechanism of firefly (beetle) bioluminescence with amino-analogs of luciferin and oxyluciferin
Takashi Hirano; Hiroyuki Nagai; Takuto Matsuhashi; Yosuke Hasumi; Satoshi Iwano; Kazuto Ito; Shojiro Maki; Haruki Niwa; Vadim R. Viviani
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, ROYAL SOC CHEMISTRY, 11, 8, 1281-1284, 2012, Peer-reviwed, Spectroscopic properties of amino-analogs of luciferin and oxyluciferin were investigated to confirm the color modulation mechanism of firefly (beetle) bioluminescence. Fluorescence solvatochromic character of aminooxyluciferin analogs indicates that the bioluminescence of aminoluciferin is useful for evaluating the polarity of a luciferase active site.
Scientific journal, English

Bioluminescence characteristics of the fruiting body of Mycena chlorophos
Kenichi Mori; Satoshi Kojima; Shojiro Maki; Takashi Hirano; Haruki Niwa
LUMINESCENCE, WILEY-BLACKWELL, 26, 6, 604-610, Nov. 2011, Peer-reviwed, Bioluminescent fungi are widely distributed on land and most belong to the class Basidomycetes. Light of about 530 nm wavelength maximum is emitted continuously. The molecular basis for the light-emitting process remains unclear. We investigated the characteristics of the bioluminescence using cultivated fruiting bodies of M. chlorophos. Only fresh fruiting bodies exhibited long-lasting light emission; rapid decay of light emission was observed with frozen and freeze-dried samples. Freeze-dried samples can be stored at room temperature under dry conditions and may be useful for the isolation of luciferin. The light emission of the fresh fruiting bodies was maintained in various buffers at varying pH; it could be stopped with pH 4 acetate buffer and could be recovered at pH 6. The isolation of luciferin from the fresh fruiting bodies might be possible by the control of buffer pH. The effect of temperature on the light emission of fruiting bodies indicated that bioluminescence in M. chlorophos may involve enzymatic reaction(s). The solubilization of bioluminescent components from the fruiting bodies could not be achieved with various surfactants. Copyright (C) 2011 John Wiley & Sons, Ltd.
Scientific journal, English

Influence of Electron-Donating and Electron-Withdrawing Substituents on the Chemiluminescence Behavior of Coelenterazine Analogs
Saito, R; Hirano, T; Maki, S; Niwa, H; M. Ohashi, M
Bull. Chem. Soc. Jpn., The Chemical Society of Japan, 84, 1, 90-99, Jan. 2011, Peer-reviwed
Scientific journal, English

Influence of Electron-Donating and Electron-Withdrawing Substituents on the Chemiluminescence Behavior of Coelenterazine Analogs
Ryota Saito; Takashi Hirano; Shojiro Maki; Haruki Niwa; Mamoru Ohashi
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 84, 1, 90-99, Jan. 2011, Peer-reviwed, Coelenterazine analogs 3a-3e possessing various substituents at the para-position of the 6-phenyl group (R = CF3, F, H, OMe, and NMe2) were synthesized, and the chemiluminescent properties of 3a-3e in dimethyl sulfoxide (DMSO) were investigated quantitatively. Chemiluminescence maxima observed in the range of 454-478 nm showed a bathochromic shift as the electron-donating ability of R increased. Chemiluminescence quantum yields (Phi(CL)) were obtained in the range of 0.0006-0.0018. The analog 3a possessing the electron-withdrawing CF3 group showed a slight decrease in its Phi(CL) value. The fluorescence quantum yields (Phi(F)) of the light emitter, 2-acetamidopyrazine anions 4a(-)-4e(-), were observed in the range of 0.005-0.21 and showed substituent dependency in that the increment in the electron-withdrawing ability of R decreases the Phi(F) value. The efficiency of generation of the singlet-excited 4a(-)-4e(-) (Phi(s)) showed a small change in the range of 0.008-0.015. From these quantitative analyses of the quantum efficiencies, we found that an electron-donating substituent R is not required for the efficient generation of a singlet-excited light emitter, but is required for the high Phi(F) of the emitter.
Scientific journal, English

Colorimetric and fluorometric sensing of the Lewis acidity of a metal ion by metal-ion complexation of imidazo[1,2-a]pyrazin-3(7H)-ones
Takashi Hirano; Takashi Sekiguchi; Daisuke Hashizume; Hiroshi Ikeda; Shojiro Maki; Haruki Niwa
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 66, 21, 3842-3848, May 2010, Peer-reviwed, Metal-ion complexation of 7-benzylimidazo[1,2-a]pyrazin-3(7H)-one derivative (2) with Li+, Mg2+, Ca2+, Ba2+, Sc3+, and La3+ in acetonitrile resulted in successive modulations of its UV/vis absorption and fluorescence spectroscopic properties. This result indicates that 2 can be used as a calorimetric and fluorometric sensor of the Lewis acidity of a metal ion in aprotic solutions. The hypothesis that the metal-ion complex has a O10(imidazopyrazinone)-metal ion bond was supported by X-ray crystallographic analysis and quantum chemical calculations for a Li+ complex of 7-methylimidazo[1,2-a]pyrazin-3(7H)-one derivative (1). (C) 2010 Elsevier Ltd. All rights reserved.
Scientific journal, English

Synthesis and properties of bis(pyrazino[2 ',3 ':4,5]imidazole)-fused 1,2,5,6-tetrahydro-1,4,5,8,9,10-hexaazaanthracenes: a new fluorescent nitrogen-rich heterocycle
Sojiro Hachiya; Daisuke Hashizume; Shojiro Maki; Haruki Niwa; Takashi Hirano
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 51, 10, 1401-1403, Mar. 2010, Peer-reviwed, Nitrogen-rich heterocycles, bis(pyrazino[2',3':4,5]imidazole)-fused 1,2,5,6-tetrahydro-1,4,5,8,9,10-hexaazaanthracenes (BPI-HAAs) were prepared by conventional Pd(OAc)(2)/BINAP-catalyzed C-N coupling reactions of 5-aryl-3-bromoaminopyrazines. The BPI-HAA core is a planar structure with aromaticity, and this heterocycle exhibits red fluorescence and moderate electron-accepting characteristics. (C) 2010 Elsevier Ltd. All rights reserved.
Scientific journal, English

Synthesis and fluorescence properties of difluoro[amidopyrazinato-O,N]boron derivatives: a new boron-containing fluorophore
Sojiro Hachiya; Takayuki Inagaki; Daisuke Hashizume; Shojiro Maki; Haruki Niwa; Takashi Hirano
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 51, 12, 1613-1615, Mar. 2010, Peer-reviwed, New boron-containing fluorophores, difluoro[amidopyrazinato-O,N]boron (APB) derivatives, were prepared from amidopyrazines. The fluorescence properties of APB were successfully modulated by an aryl substitution at the C8 position. (C) 2010 Elsevier Ltd. All rights reserved.
Scientific journal, English

Distinction of Sialyl Anomers on ESI- and FAB-MS/MS: Stereo-Specific Fragmentations
Yoko Ohashi; Masayuki Kubota; Hiroshi Hatase; Mitsuhiro Nakamura; Takashi Hirano; Haruki Niwa; Yoshitaka Nagai
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, ELSEVIER SCIENCE INC, 20, 3, 394-397, Mar. 2009, Peer-reviwed, An anomeric pair of the lysoglyceroganglioside 1-O-octadecyl-3-O-(N-acetyl)neuraminyl-sn-glycerol sodium salt was studied to see if sialic anomers were distinguishable by mass spectra. It was evident that, in the electrospray ionization and fast-atom bombardment product-ion spectra: (1) in the positive MS(2) product-ion spectrum, the beta- anomer showed an unexpected aglycone-side sodiated sodium alkoxide ion, which was absent for the a-anomer; (2) in both polarities the beta-anomer showed dehydration much more easily than the a-anomer; and (3) in the negative MS(2) product-ion spectrum, the P-anomer also readily showed decarboxylation. Our hypothesis is that, although several easily interconvertible conformations may be allowed, the one having the large aglycone in the equatorial orientation affects the collision-induced dissociation fragmentations. (J Am Soc Mass Spectrom 2009, 20, 394-397) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry
Scientific journal, English

Spectroscopic Studies of the Light-Color Modulation Mechanism of Firefly (Beetle) Bioluminescence
Takashi Hirano; Yosuke Hasumi; Kazuhiro Ohtsuka; Shojiro Maki; Haruki Niwa; Minoru Yamaji; Daisuke Hashizume
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMER CHEMICAL SOC, 131, 6, 2385-2396, Feb. 2009, Peer-reviwed, To reveal the light-color modulation mechanism of firefly (beetle) bioluminescence, we investigated the spectroscopic properties of the phenolate anion 1-O- generated from 5,5-dimethyloxyluciferin (1-OH) using various base/solvent combinations. Phenolate anion 1-O- is a model compound for the keto form of wild-type oxyluciferin phenolate anion (OL-), which is postulated to be the emitter of the bioluminescence. The fluorescence maxima of 1-O- were found to depend on the base/solvent combination used, and they varied in the range 541-640 nm, which covers the almost whole range of the bioluminescence emission maximum. In a polar solvent, where (1)(1-O-)* and the countercation (the conjugate acid of a base) make a solvent-separated ion pair or a free ion couple, the emission maxima of 1-O- were found to be modulated by the solvent polarity. In a less polar solvent, where (1)(1-O-)* and the countercation are formed as a contact ion pair, the strength of the covalent character of the O8'center dot center dot center dot H bond between (1)(1-O-)* and the countercation is operative. The effect of the base/solvent combination on the emission properties of (1)(1-O-)* was also verified using fluorescence lifetime measurements and density functional theory calculations on 1-O- and its ion-pair models. On the basis of these results, we propose the following light-color modulation mechanism: (1) the light emitter is the excited singlet state of OL- [ (1)(OL-)*], and (2) light emission from (1)(OL-)* is modulated by the polarity of the active-site environment of a luciferase and the degree of covalent character of the O8'center dot center dot center dot H bond between (1)(OL-)* and a protonated basic moiety in the active site. Mechanisms for variation of the bioluminescence colors and their applications are discussed.
Scientific journal, English

CHEMIEXCITATION MECHANISM FOR CYPRIDINA (VARGULA) AND AEQUOREA BIOLUMINESCENCE
T. Hirano; H. Ohba; Y. Takahashi; S. Maki; S. Kojima; H. Ikeda; H. Niwa
BIOLUMINESCENCE AND CHEMILUMINESCENCE, WORLD SCIENTIFIC PUBL CO PTE LTD, 19-22, 2009, Peer-reviwed
International conference proceedings, English

The reaction mechanism for the high quantum yield of Cypridina (Vargula) bioluminescence supported by the chemiluminescence of 6-aryl-2-methylimidazo[1,2-a]pyrazin-3(7H)-ones (Cypridina luciferin analogues)
Takashi Hirano; Yuto Takahashi; Hiroyuki Kondo; Shojiro Maki; Satoshi Kojima; Hiroshi Ikeda; Haruki Niwa
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, ROYAL SOC CHEMISTRY, 7, 2, 197-207, 2008, Peer-reviwed, To establish the reaction mechanism of the high-quantum-yield bioluminescence in Cypridina (Vargula), we investigated the chemiluminescence of 6-aryl-2-methylimidazo[1,2-a] pyrazin-3(7H)-ones (1H) as Cypridina luciferin analogues in DMSO-1,1,3,3-tetramethylguanidine and in diglyme-acetate buffer. We found that the chemiluminescence of 1H with an electron-donating aryl group, such as a 4-(dimethylamino) phenyl, 3-indolyl or 3-(1-methyl) indolyl group, gave a high quantum yield (Phi(CL)) in diglymeacetate buffer. This indicates that the reaction mechanism producing this high Phi(CL) involves the chemiexcitation of a neutral dioxetanone intermediate possessing an electron-donating aryl group to the singlet excited state of neutral acetamidopyrazine (the light emitter). In addition, we investigated the. fluorescence of acetamidopyrazines and performed DFT calculations for neutral dioxetanones and the transition states (TS) of the dioxetanone's decomposition. The results made it clear that the electron-donating aryl group gives the TS and the singlet-excited acetamidopyrazine (S-1) a strong intramolecular charge transfer (ICT) character, and their similar ICT character leads to the ICT TS -> S-1 route in the charge transfer-induced luminescence (CTIL) mechanism for efficient chemiexcitation. The reaction mechanism of the chemiluminescence of 1H can explain the highly efficient chemiexcitation of Cypridina bioluminescence.
Scientific journal, English

Electrolysis and its hybrid methods applied to decomposition of endocrine disrupting chemicals
Naomi Takagami; Kazuhiro Ohtsuki; Shojiro Maki; Haruki Niwa; Shin-ichi Hatanaka; Shigeo Hayashi
ELECTROCHEMISTRY, ELECTROCHEMICAL SOC JAPAN, 74, 8, 599-602, Aug. 2006, Peer-reviwed, Rate constants for decomposition reaction were measured for several phenols, i.e., bisphenol A, p-chlorophenol, p-octylphenol, 2,4-dichlorophenol, p-tert-butylphenol and for two other chemicals, benzophenone and PCB compounds in waste oil. The following methods were adopted: electrolysis, photolysis, sonolysis, photolytic electrolysis, and sonolytic electrolysis. The initial concentration was fixed at 50 mg/L except for the PCB, for which the concentration for all the isomers was 500 ng/L. The solvent was water, but for chemicals with insufficient solubility, mixtures with alcohols were used. Additional application of ultrasound led to remarkable enhancement for p-chlorophenol and 2,4-dichlorophenol. The electrolysis rate constant for PCB compounds was comparable to that for the phenols. Benzophenone was decomposed 10 times as slow as the phenols partly because of the solvent containing alcohols.
Scientific journal, English

Chemiluminescence of 6-aryl-2-methylimidazo[1,2-a]pyrazin-3(7H)-ones in DMSO/TMG and in diglyme/acetate buffer: support for the chemiexcitation process to generate the singlet-excited state of neutral oxyluciferin in a high quantum yield in the Cypridina (Vargula) bioluminescence mechanism
Yuto Takahashi; Hiroyuki Kondo; Shojiro Maki; Haruki Niwa; Hiroshi Ikeda; Takashi Hirano
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 47, 34, 6057-6061, Aug. 2006, Peer-reviwed, The chemiluminescence of 6-aryl-2-methylimidazo [1,2-a]pyrazin-3 (7 H) -ones (Cypridina luciferin analogues) in DMSO/ 1,1,3,3-tetramethylguanidine and in diglyme/acetate buffer was investigated. The results indicate that the reaction mechanism that produces a high chemiluminescence quantum yield involves a chemiexcitation process from a neutral dioxetanone intermediate possessing an electron-donating aryl group (sigma(Ar) <-0.6) to the singlet-excited state of neutral acetamidopyrazine. This result may be applied to the reaction mechanism for Cypridina (Vargula) bioluminescence. (c) 2006 Elsevier Ltd. All rights reserved.
Scientific journal, English

Real light emitter in the bioluminescence of the calcium-activated photoproteins aequorin and obelin: light emission from the singlet-excited state of coelenteramide phenolate anion in a contact ion pair
Kotaro Mori; Shojiro Maki; Haruki Niwa; Hiroshi Ikeda; Takashi Hirano
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 62, 26, 6272-6288, Jun. 2006, Peer-reviwed, Fluorescence of the phenolate anion (3(O)(-)) and the amide anion (5(N)(-)) of coelenteramide analogues in ion pairs with various counter cations was systematically investigated to elucidate the ionic structure of the light emitter in the bioluminescence of the calcium-activated photoproteins aequorin and obelin. The fluorescent properties of 3(O)- in an ion pair with a conjugate acid of an organic base (BASE-H+) were varied depending on the structural variation of the ion pair and the solvent polarity. In particular, the fluorescence of 3(O)- in the ion pair with the conjugate acid of n-butylamine (NBA-H+) indicates that the singlet-excited state of 3(O)(-) ((1)3(O)(-)*) and NBA-H+ make a contact ion pair in which the fluorescence emission maxima of 3(O)- is sensitive to the solvent polarity and the fluorescence quantum yields of 3(O)- increase in a less polar solvent. The results also confirm that (1)3(O)-* is a twisted intramolecular charge transfer state. By contrast, the fluorescence of 5(N)(-) in an ion pair depends little on the BASE-H+ or the solvent polarity. Based on these results, we conclude that the light emitter in aequorin and obelin bioluminescences is the singlet-excited state of coelenteramide phenolate anion 2(O)(-)((1)2(O)(-)*) in a contact ion pair with an imidazolium side chain of a histidine residue, which is located at the less polar active sites of the photoproteins. We also propose a mechanism for the bioluminescence reaction, including the chemiexcitation process to give (1)2(O)(-)*. (c) 2006 Elsevier Ltd. All rights reserved.
Scientific journal, English

Construction of a New Firefly Bioluminescence System using L-luciferin
Mitsuhiro Nakamura; Kazuki Niwa; Shojiro Maki; Takashi Hirano; Yoshihiro Ohmiya; Haruki Niwa
Tetrahedron Letters, 47, 7, pp. 1197-1200, 2006, Peer-reviwed
Scientific journal, English

Substituent effects on the kinetics for the chemiluminescence reaction of 6-arylimidazo[1,2-a]pyrazin-3(7H)-ones (Cypridina luciferin analogues): support for the single electron transfer (SET)-oxygenation mechanism with triplet molecular oxygen
H Kondo; T Igarashi; S Maki; H Niwa; H Ikeda; T Hirano
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 46, 45, 7701-7704, Nov. 2005, Peer-reviwed, Kinetics of chemiluminescence reactions of 2-methyl-6-phenylimidazo[1,2-a]pyrazin-3 (7H)-one (1c, Cypridina luciferin analogue) and substituent effects of the 6-aryl group of derivatives 1 strongly suggest that the rate-determining step is a single electron transfer from an anion derived from 1 to a triplet molecular oxygen (O-2) in the oxygenation process. (c) 2005 Elsevier Ltd. All rights reserved.
Scientific journal, English

Substituent effects on the spectroscopic properties of solvatochromic 2-phenylimidazo[1,2-a]pyrazin-3(7H)-ones: an effective control for the colorimetric sensor properties
Y Takamuki; S Maki; H Niwa; H Ikeda; T Hirano
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 61, 42, 10073-10080, Oct. 2005, Peer-reviwed, Substituent effects on the spectroscopic properties of a solvatochromic compound, 7-methyl-2-phenylimidazo[1,2-a]pyrazin-3(7H)-one (1c), using derivatives 1 with a para-substituent R on the phenyl group, were investigated systematically. In the UV/visible absorption spectra, the solvatochromic property of I originating from hydrogen-bonding interactions was effectively regulated by the substituent effects. In particular, the cyano derivative le showed significant solvatochromism with a wide color variation range and a high sensitivity toward solvents. Similarly, the fluorescence of I showed a redshift as the electron-withdrawing property of R increased. The substituent effects were evaluated by AM1-COSMO calculations, which also suggested that derivatives 1 are good electron donors and that the electron-donating ability is regulated by R. This was confirmed by the observation of low oxidation potentials and the formation of charge-transfer complexes with tetracyanoethylene. Absorption-spectrum changes of le and le caused by metal-ion complexation were also compared, showing that the cyano derivative le is a good colorimetric sensor for the Lewis acidity of the metal ions. From these observations, it was established that para-substitution of R on the phenyl group of le caused successive modulations of the colorimetric sensor properties. (c) 2005 Elsevier Ltd. All rights reserved.
Scientific journal, English

Bioluminescence in the limpet-like snail Latia neritoides.
Yoshihiro Ohmiya; Satoshi Kojima; Mitsuhiro Nakamura; Haruki Niwa
Bull. Chem. Soc. Jpn., 78, 7, pp. 1197-1205, Jul. 2005, Peer-reviwed
Scientific journal, English

Firefly luciferase exhibits bimodal action depending on the luciferin chirality
M Nakamura; S Maki; Y Amano; Y Ohkita; K Niwa; T Hirano; Y Ohmiya; H Niwa
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ACADEMIC PRESS INC ELSEVIER SCIENCE, 331, 2, 471-475, Jun. 2005, Peer-reviwed, Firefly luciferase is able to convert (L)-luciferin into luciferyl-CoA even under ordinary aerobic luciferin-luciferase reaction conditions. The luciferase is able to recognize strictly the chirality of the luciferin structure, serving as the acyl-CoA synthetase for (L)-luciferin, whereas (D)-luciferin is used for the bioluminescence reaction. (D)-Luciferin inhibits the luciferyl-CoA synthetase activity Of (L)-luciferin, whereas (L)-luciferin retards the bioluminescence reaction Of (D)-luciferin, meaning that both enzyme activities are prevented by the enantiomer of its own substrate. © 2005 Elsevier Inc. All rights reserved.
Scientific journal, English

Electron-transfer oxygenation mechanism in the chemiluminescence reaction of imidazo[1,2-a]pyrazin-3(7H)-one with triplet dioxygen
Hiroyuki Kondo; Takayuki Igarashi; Shojiro Maki; Haruki Niwa; Hiroshi Ikeda; Takashi Hirano
Tetrahedron Letters, 46, 7701-7704, 2005, Peer-reviwed, ウミホタル生物発光反応を確立するため，６位のフェニル基上に種々置換基を導入した誘導体を用いて，詳細な化学発光反応の速度論を解析した．この結果，反応機構中，酸素化過程が電子移動によって支配されていることを明らかにした．
Scientific journal, English

Characterization of [1-13C]-Specifically Labeled Amino Acids Using ESIMS/MS in the Selected Reaction Monitoring Mode
Yoko Ohashi; Hiroshi Hatase; Mitsuhiro Nakamura; Takashi Hirano; Shojiro Maki; Haruki Niwa
Journal of the Mass Spectrometry Society of Japan, the Mass Spectrometry Society of Japan, 53, 309-314, 2005, Peer-reviwed
Scientific journal, English

6,8-diarylimbazo[1, 2-a]pyrazin-3(7H) - Ones as potential chemiluminescent pH/superoxide double sensors
R Saito; N Suga; A Katoh; S Maki; T Hirano; H Niwa
Bioluminescence & Chemiluminescence: Progress and Perspectives, WORLD SCIENTIFIC PUBL CO PTE LTD, 335-338, 2005, Peer-reviwed
International conference proceedings, English

Development of the chemistry of the imidazopyrazionone-bioluminescence system: From the bio- and chemiluminescence mechanism to a design of sensor molecules
T Hirano; S Nakai; S Sekiguchi; S Fujio; S Maki; H Niwa
Bioluminescence & Chemiluminescence: Progress and Perspectives, WORLD SCIENTIFIC PUBL CO PTE LTD, 117-120, 2005, Peer-reviwed
International conference proceedings, English

Bioluminescence activity of Latia luciferin analogues: replacement of the 2,6,6-trimethylcyclohexene ring onto the methyl-substituted phenyl groups
M Nakamura; M Mamino; M Masaki; S Maki; R Matsui; S Kojima; T Hirano; Y Ohmiya; H Niwa
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 46, 1, 53-56, Jan. 2005, Peer-reviwed, A series of Latia luciferin analogues having methyl-substituted phenyl groups instead of the natural 2.6.6-trimethylhexene ring was synthesized and their bioluminescence activity were measured. The Latia luciferase was found to be able to moderately recognize the appropriately methyl-substituted phenyl analogues with the same light production kinetics as. that of natural luciferin. (C) 2004 Elsevier Ltd. All rights reserved.
Scientific journal, English

Characterization of Regio-specific 13CO-Labeling of Amino Acids Using ESIMS/MS in the SRM Mode.
Yoko OHASHI; Hiroshi HATASE; Mitsuhiro NAKAMURA; Takashi HIRANO; Shojiro MAKI; Haruki NIWA
J. Mass Spectrom. Soc. jpn, 53, 6, pp. 309-314, 2005, Peer-reviwed
Scientific journal, English

Substituent effects on the solvatochromism of 2-phenylimidazopyrazinones: Effective control of the color variation range and sensitivity toward an indication of the proton-donor ability of solvents by an electron-withdrawing group substitution
Y Takamuki; S Maki; H Niwa; H Ikeda; T Hirano
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 33, 11, 1484-1485, Nov. 2004, Peer-reviwed, A para-substitution on the phenyl group of 2-phenylimida-zopyrazinone successively resulted in a change of the solvato-chromic property, especially of the color-variation range and sensitivity to solvents, demonstrating that derivatives possessing an electron-withdrawing group are preferable as potential indicators of the proton-donor ability of solvents.
Scientific journal, English

Regioselective phenyl-substitution effects on the solvatochromism of 2-phenylimidazo[1,2-a]pyrazin-3(7H)-one derivatives: Expansion of the color variation range of a visible indicator for the proton donor ability of solvents.
Shunsuke Fujio; Daisuke Hashizume; Yoshiharu Takamuki; Masanori Yasui; Fujiko Iwasaki; Shojiro Maki; Haruki Niwa; Hiroshi Ikeda; Takashi Hirano
Tetrahedron Letters, 45, 46, pp. 8531-8534, Oct. 2004, Peer-reviwed
Scientific journal, English

Synthesis of prostaglandin F ethanolamide by prostaglandin F synthase and identification of Bimatoprost as a potent inhibitor of the enzyme: new enzyme assay method using LC/ESI/MS
N Koda; Y Tsutsui; H Niwa; S Ito; DF Woodward; K Watanabe
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, ELSEVIER SCIENCE INC, 424, 2, 128-136, Apr. 2004, Peer-reviwed, Prostaglandin (PG) D-2 ethanolamide (prostamide D-2) was reduced to 9alpha, 11beta-PGF(2) ethanolamide (9alpha, 11beta-prostamide F-2) by PGF synthase, which also catalyzes the reduction of PGH(2) and PGD(2) to PGF(2alpha) and 9alpha11beta-PGF(2), respectively. These enzyme activities were measured by a new method, the liquid chromatographic-electrospray ionization-mass spectrometry (LC/ESI/MS) technique, which could simultaneously detect the substrate and all products. PGF(2alpha), 9alpha,l lbeta-PGF(2), PGD(2), PGH(2), 9alpha,11beta-prostamide F-2, and prostamide D-2 were separated on a TSKgel ODS 80Ts column, ionized by electrospray, and detected in the negative mode. Selected ion monitoring (SIM) of m/z 353 ([M-H](-)), 353 ([M-H](-)), 351 ([M-H](-)) 333 ([M-H-H2O](-)) 456 ([M+59](-)), and m/z 358 ([M-37](-)) was used for quantifying PGF(2alpha), 9alpha,11beta-PGF(2), PGD(2), PGH(2), 9alpha,11beta-prostamide F-2, and prostamide D-2, respectively. The detection limit for PGF(2alpha) and 9alpha,11beta-PGF(2) was 0.01 pmol, that for PGH(2) and PGD(2), 0.1 pmol; and that for prostamide D-2 and 9alpha,11beta-prostamide F-2, 0.5 and 0.03 pmol, respectively. The LC/ESI/MS technique for measuring PGF synthase activity showed higher sensitivity than other methods. Using this method, we found that Bimatoprost, the ethyl amide analog of 17-phenyl-trinor PGF(2alpha) and an anti-glaucoma agent, inhibited all three reductase activities of PGF synthase when used at a low concentration. These results suggest that Bimatoprost also behaves as a potent PGF synthase inhibitor in addition to having prostamide-like activity. (C) 2004 Elsevier Inc. All rights reserved.
Scientific journal, English

Synthesis of Latia Luciferin Benzoate Analogues and those Bioluminescent Activity.
Mitsuhiro Nakamura; Mizuki Masaki; Shojiro Maki; Ryo Matsui; Minako Hieda; Masashi Mamino; Takashi Hirano; Yoshihiro Ohmiya; Haruki Niwa
Tetrahedron Letters, 45, 10, pp. 2203-2205, Feb. 2004, Peer-reviwed
Scientific journal, English

Analysis of sugar epimers using mass spectrometry: N-acetyllactosamine-6,6 '-disulfate and the 2 '-epimer
Y Ohashi; Y Itoh; M Kubota; K Hamada; M Ohashi; T Hirano; H Niwa
EUROPEAN JOURNAL OF MASS SPECTROMETRY, IM PUBLICATIONS, 10, 2, 269-278, 2004, Peer-reviwed, Galbeta1-4GlcNAc-6,6'-disulfate and 2'-epimer corresponding to Galbeta1-4ManNAc-6,6'-disulfate were distinguished by mass spectrometry by utilizing fast atom bombardment (FAB), electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) methods. As for the steric information, negative-ion ESI mass spectrometry/mass spectrometry (MS/MS) provides the most extensive data, but FAB MS/MS also reveals detailed structural information of interest in our case, where MALDI MS is not yet fully equipped with post-source decay.
Scientific journal, English

Metal-ion complexation of imidazo[1,2-a]pyrazin-3(7H)-ones: continuous changes in absorption spectra of complexes depending on the Lewis acidity of the metal ion
T Sekiguchi; S Maki; H Niwa; H Ikeda; T Hirano
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 45, 5, 1065-1069, Jan. 2004, Peer-reviwed, The spectroscopic properties of metal-ion complexes of several imidazopyrazinone derivatives with Li+, Mg2+, Ca2+, Ba2+, Sc3+, and La3+ ions were studied. The spectral characteristics and the formation constants of the complexes changed continuously depending on the Lewis acidity of the metal ion, suggesting that the imidazopyrazinones can find application as indicators of Lewis acidity. In the case of bis-imidazopyrazinone derivatives, the complexation abilities were enhanced by chelate effects. (C) 2003 Elsevier Ltd. All rights reserved.
Scientific journal, English

Fundamental studies on the structures and spectroscopic properties of imidazo[1,2-a]pyrazin-3(7H)-one derivatives
S Nakai; M Yasui; M Nakazato; F Iwasaki; S Maki; H Niwa; M Ohashi; T Hirano
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 76, 12, 2361-2387, Dec. 2003, Peer-reviwed, The fundamental physical properties of 2-methyl and 2-phenylimidazo[1,2-a]pyrazin-3(7H)-one 1 and 2, and their N- and O-alkylated derivatives 3-6 have been investigated by X-ray crystallography, UV/vis absorption spectroscopy, NMR, and AMl-COSMO calculations. The crystal structures of 3 and 4 showed that the imidazo[1,2-a]pyrazin-3(7H)-one (imidazopyrazinone) pi-system has a planar ring structure and a weakened carbonyl character of the C3-O10 bond, suggesting that the imidazopyrazinone pi-system has the character of a zwitter-ionic resonance structure to increase the aromaticity. The data concerning the bond length alternations and the NMR chemical shifts of 1-4 also support that their imidazopyrazinone rings have small portions of aromatic character. In addition, imidazopyrazinone derivatives 1-4 showed solvatochromism originating by hydrogen-bonding interactions with hydrogen-bond donor solvent molecules; derivatives 1 and 2 prefer to be the NH form isomers in their tautomeric equilibriums. These observations were consistently evaluated by MO calculations. The physical properties of protonated species of 1-6 and anion species of 1 and 2 were also established. The fundamental properties of the imidazopyrazinone pi-system explain the several problems of the chemi- and bioluminescence reactivities of imidazopyrazi none derivatives and of the construction of a bioluminescent supramolecule.
Scientific journal, English

Essential (110)Cys in active site of membrane-associated prostaglandin E synthase-2
K Watanabe; H Ohkubo; H Niwa; N Tanikawa; N Koda; S Ito; Y Ohmiya
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ACADEMIC PRESS INC ELSEVIER SCIENCE, 306, 2, 577-581, Jun. 2003, Peer-reviwed, The amino acid sequence of membrane-associated prostaglandin (PG) E synthase-2 (mPGE synthase-2), which has a broad specificity in its thiol requirement for a catalytic activity, has the consensus region from (104)Leu to (120)Leu found in glutaredoxin and of thioredoxin. The sequence of Cys-x-x-Cys in the consensus region is the active site for thioredoxin and mPGE synthase-2 also has this amino acid sequence ((110)Cys-x-x-(113)Cys). The mutation from (110)Cys to Ser or the double mutation from (110)Cys and (113)Cys to Ser caused loss of PGE synthase activity, whereas the single mutation from (110)Cys to Ser did not affect the enzyme activity. These results indicate that (110)Cys, but not (113)Cys, is the essential amino acid in the active site of mPGE synthase-2. (110)Cys is an important amino acid in PGE synthase activity and plays the critical role as Cys at the same position in redoxin. Moreover, we found that the reduced form of lipoic acid (dihydrolipoic acid) serves as one of the natural activators of mPGE synthase-2 in the cells. (C) 2003 Elsevier Science (USA). All rights reserved.
Scientific journal, English

Pd black deposited on polypropylene sheet as a highly selective catalyst for hydrogenation of alkenes
S Maki; M Okawa; T Makii; T Hirano; H Niwa
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 44, 18, 3717-3721, Apr. 2003, Peer-reviwed, A catalyst deposited on a polypropylene sheet having an activity of almost the same level as commercially available Pd black and capable of promoting hydrogenolysis-free hydrogenation was developed. (C) 2003 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

Hydrogenolysis-free Hydrogenation Using Pd Black Catalyst Deposited on Pd Sheet.
Shojiro Maki; Makiko Okawa; Toshimichi Makii; Takashi Hirano; Haruki Niwa
ITE Letters on Batteries, New Technologies and Medicine, 4, 1, pp. 49-54, 2003, Peer-reviwed
Scientific journal, English

Viscosity-dependent fluorescence decay of the GFP chromophore in solution due to fast internal conversion
AD Kummer; C Kompa; H Niwa; T Hirano; S Kojima; ME Michel-Beyerle
JOURNAL OF PHYSICAL CHEMISTRY B, AMER CHEMICAL SOC, 106, 30, 7554-7559, Aug. 2002, Peer-reviwed, Time-resolved fluorescence measurements at 275 K show that the excited-state lifetime of a model chromophore of the green fluorescent protein (GFP) substantially increases from subpicoseconds in low-viscosity solvents such as ethanol (eta = 1.7 cP) to 30 ps in glycerol (eta = 9.9 x 10(3) cP) and reaches 2.1 ns in glycerol glass at 150 K. At high temperatures the similarity of excited-state decay and ground-state recovery kinetics indicates internal conversion being responsible for the short fluorescence lifetimes. Their viscosity dependence reflects on a motion with a considerable amplitude that is damped by viscous drag and outweighs thermal activation as is concluded from measurements at different temperatures. In solution the neutral and the anionic forms of the model chromophore are similarly nonfluorescent in contrast to wild-type GFP and mutants where the deprotonated form is hardly undergoing internal conversion. Thus, the protein selectively restricts motional degrees of freedom of the chromophore in specific protonation states.
Scientific journal, English

Preparation of deoxygenated derivatives of neoanisatin, a neurotoxic sesquiterpenoid having a beta-lactone
K Obitsu; S Maki; T Hirano; H Niwa
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 75, 2, 347-354, Feb. 2002, Peer-reviwed, Seven deoxygenated neoanisatin derivatives were prepared from anisatin and neoanisatin by utilizing methoxalyl ester/tributylstannane (n-Bu3SnH) deoxygenation procedure coupled with a novel dehydration reaction of neoanisatin.
Scientific journal, English

Reduction in Desorption Mass Spectrometry: Multiple Protonation on Flavins without Charge Increment.
Yoshiyuki Itoh; Yoko Ohashi; Toshimichi Shibue; Akio Hayashi; Shojiro Maki; Takashi Hirano; Haruki Niwa
J. Mass Spectrom. Jpn., 50, 2, pp. 52-57, 2002, Peer-reviwed
Scientific journal, English

Preparation and Toxic Property of Carbapicrotoxinin, a Cyclopropane-containing Analog of a GABA-antagonistic Sesquiterpenoid Picrotoxinin.
Kazuyoshi Obitsu; Shojiro Maki; Takashi Hirano; Haruki Niwa
ITE Letters on Batteries, New Technologies and Medicine, 3, 3, pp. 358-361, 2002, Peer-reviwed
Scientific journal, English

Fluorescence properties of phenolate anions of coelenteramide analogues: the light-emitter structure in aequorin bioluminescence
Y Imai; T Shibata; S Maki; H Niwa; M Ohashi; T Hirano
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY, ELSEVIER SCIENCE SA, 146, 1-2, 95-107, Dec. 2001, Peer-reviwed, To elucidate the ionic structure of the excited state of light-emitter coelenteramide in aequorin bioluminescence, the fluorescent properties of phenolate anions of coelenteramide analogues were investigated. Fluorescence of phenolate anion in non-polar solvents was observed by electronic excitation of a 1: 1 hydrogen-bonded complex of a coelenteramide analogue with a hydrogen-bond donor molecule such as n-butylamine. In polar solvents, the phenolate anion was directly generated using a base, and its fluorescence was studied. These results confirm that the singlet-excited state of phenolate anion of coelenteramide has an intramolecular CT character, and that its fluorescence emission wavelength changes depending upon solvent polarity. The fluoro-substituent effect on the fluorescent property of phenolate anions was also clarified to help in explaining the bioluminescent property of fluorinated semi-synthetic aequorin. These results consistently support the assignment that the phenolate anion is the ionic structure of the excited light-emitter in BFP during AQ bioluminescence. (C) 2001 Elsevier Science B.V. All rights reserved.
Scientific journal, English

Effect of solvent and hydrogen during selective hydrogenation
S Maki; Y Harada; R Matsui; M Okawa; T Hirano; H Niwa; M Koizumi; Y Nishiki; T Furuta; H Inoue; C Iwakura
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 42, 47, 8323-8327, Nov. 2001, Peer-reviwed, Described is the solvent effect for the chemoselective hydrogenation of alkenes having a benzyloxy group (Bn-O-) using a hydrogenation system employing atomic hydrogen permeating through a Pd sheet electrode. (C) 2001 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

Hydrogenolysis-free hydrogenation by Pd black powder catalyst
S Maki; M Okawa; R Matsui; T Hirano; H Niwa
SYNLETT, GEORG THIEME VERLAG KG, 10, 1590-1592, Oct. 2001, Peer-reviwed, A new general method of hydrogenolysis-free hydrogenation using a commercially available Pd black powder catalyst has developed.
Scientific journal, English

Purification and Properties of the Luciferase from the Marine Ostracod Vargula hilgendorfii.
Koji Kobayashi; Yoshihiro Ohmiya; Daisaku Shinohala; Takuji Nabetani; Haruki Niwa
"Bioluminescence and Chemiluminescence," ed by J. F. Case, P. J. Herring, B. H. Robinson, S. H. D. Haddock, L. J. Kricka, and P. E. Stanley: World Scientific, Singapore, World Scientific, Singapore, 87-90, 2001, Peer-reviwed
International conference proceedings, English

Improved Syntheses of Watasenia Preluciferin (Coelenterazine) and Watasenia Luciferin (Coelenterazine Disulfate), and Site Specific Syntheses of the Coelenterazine Monosulfates.
Satoshi Kojima; Shojiro Maki; Takashi Hirano; Haruki Niwa; Mamoru Ohashi; Frederick I. Tsuji
ITE Letters on Batteries, New Technologies and Medicine, 2, 3, pp. C1-C5, 2001, Peer-reviwed
Scientific journal, English

Intramolecular electron-transfer-induced cleavage of dioxetanes observed in fast-atom bombardment tandem mass spectrometry
M Ohashi; M Takanashi; N Watanabe; M Matsumoto; T Saisu; H Niwa
EUROPEAN JOURNAL OF MASS SPECTROMETRY, IM PUBLICATIONS, 7, 6, 441-445, 2001, Peer-reviwed, Phenolic spiroadamantyl-substituted dioxetanes are well known base-induced chemiluminescent compounds. Fast-atom bombardment collision-induced dissociation tandem mass spectrometry (FAB CID-MS/MS) of five phenolic spiroadamantyl-substituted dioxetanes in the negative-ion mode clearly showed that a highly efficient cleavage of the dioxetane rings took place to produce the corresponding phenolate ion almost exclusively. The mass spectrometric behavior of these compounds reflects the highly efficient intramolecular electron-transfer-induced cleavage of dioxetane rings, which participates in the highly efficient base-triggered chemiluminescent reactions of these compounds in solution.
Scientific journal, English

Isoquinoline formation by a novel photochemical intermolecular cycloaddition of 1,1-diphenylethene derivatives to 1,4-dicyanobenzene
H Ishii; Y Imai; T Hirano; S Maki; H Niwa; M Ohashi
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 41, 33, 6467-6471, Aug. 2000, Peer-reviwed, Phenanthrene-sensitized photoreaction of 1,1-diphenylethene (DPE) derivatives and 1,4-dicyanobenzene (DCNB) in benzene leads to a novel intermolecular cycloaddition to give isoquinoline derivatives as a novel synthetic method. The feasibility of this reaction was dependent upon the side chain structure of DPE derivatives, which would regulate the stability of radical cation DPE+. in a highly polar exciplex, and/or a contact radical ion pair, by hyperconjugation or neighboring group participation. (C) 2000 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

2,3,3a,4,9,9a-Hexahydro-9-phenyl-benzo[f]indene derivatives
D Hashizume; N Takashima; T Oikawa; H Ishii; H Niwa; F Iwasaki
ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, MUNKSGAARD INT PUBL LTD, 56, 827-829, Jul. 2000, Peer-reviwed, The title compounds, 3a,9a-trans-9,9a-trans-4,4-dimethyl-9-phenyl-2,3,3a,4,9,9a-hexahydrobenzo[f]indene, C21H24, (I), and 3a,4-trans-3a,9a-cis-9,9a-trans-4-methoxy-9-phenyl-2,3,3a,4,9,9a-hexahydrobenzo[f]indene, C20H22 O, (II), are products of the photoinduced electron-transfer reaction of 1,1-diphenyl-1,n-alkadienes. The molecular structures are in good agreement with those proposed from the reaction mechanisms. The central rings of the fused systems of both compounds take chair and boat conformations in (I) and (II), respectively. There are no remarkable short contacts shorter than the sum of the van der Waals radii in the crystals, but some weak C-H ...pi interactions are found.
Scientific journal, English

Bioluminescence activity of Latia luciferin analogs
S Kojima; S Maki; T Hirano; Y Ohmiya; H Niwa
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 41, 22, 4409-4413, Jun. 2000, Peer-reviwed, Latia luciferin analogs were synthesized and their bioluminescence activities were measured. The Latia luciferase was found to recognize strictly the 2,6,6-trimethylcyclohexene ring moiety in the luciferin structure. While the enol ether analogs exhibited no bioluminescence activity, the corresponding enol acetate analog possessed 60% activity compared to natural luciferin having an enol formate structure, implying that the initial step of the light producing reaction is an enzymatic hydrolysis to yield the corresponding enolate anion. (C) 2000 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using an inorganic particle matrix for small molecule analysis
T Kinumi; T Saisu; M Takayama; H Niwa
JOURNAL OF MASS SPECTROMETRY, JOHN WILEY & SONS LTD, 35, 3, 417-422, Mar. 2000, Peer-reviwed, Fine metal or metal oxide powder as an alternative to conventional organic matrices in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) has been utilized successfully for lower molecular mass analytes, poly(ethylene glycol) 200 (PEG 200) and methyl stearate. Eleven kinds of particle, Al, Mn, Mo, Si, Sn, SnO2, TiO2, W, WO3, Zn and ZnO, were evaluated. The analyte was mixed with a metal or metal oxide powder (inorganic matrix) with particle diameter of tens of micrometers and liquid dispersant, followed by application to the sample target. Using a commercial MALDI-TOFRMS instrument equipped with an internal 337 nm pulsed nitrogen laser, the analytes, PEG 200 and methyl stearate, were ionized as the alkali metal ion adducted molecules [hl + Na](+) or [M + K](+) when the inorganic matrices Mn, Mo, Si, Sn, TiO2, W, WO3, Zn or ZnO were used. In the case of an Al matrix, PEG 200 was ionized as [hl + K]+, whereas methyl stearate was ionized as [M + H](+) and [M + Al](+). These particles have potential as the matrix for MALDI. During our examination, however, only SnO2 particles did not ionize either PEG 200 or methyl stearate. Based on our protocol, when TiO2 powder was suspended with Liquid paraffin, PEG 200 and methyl stearate gave their MALDI-TOF mass spectra with the lowest background noise and highest intensity. TiO2 powder seemed to be a broad potential matrix for low molecular mass polar or non-polar analytes. The results suggested that bulk particles caused rapid heating/vaporization processes and ionized analyte molecules under irradiation with a pulsed W laser. The present method can be readily applied to obtain the low background noise MALDI-TOF mass spectra of small-sized compounds. Copyright (C) 2000 John Whey gi Sons, Ltd.
Scientific journal, English

Synthesis, chemi- and bioluminescence properties, and photolysis of a coelenterazine analogue having a photoreactive azido group
Jing Ling Zheng; Feng Qi Chen; Takashi Hirano; Yoshihiro Ohmiya; Shojiro Maki; Haruki Niwa; Mamoru Ohashi
Bulletin of the Chemical Society of Japan, 73, 2, 465-469, Feb. 2000, Peer-reviwed, A photoreactive analogue of coelenterazine having an azido group was synthesized. The analogue showed similar chemi- and bioluminescence properties to those of the natural coelenterazine. Photolysis of the analogue in the presence of diethylamine gave a derivative azepine as the major product.
Scientific journal, English

Synthesis and Chemi-and Bio-luminescence Properties of a Photolabile Coelenterazine Analogue Bearing an Azido Group.
Zheng, J. L; Chen, F. Q; Hirano, T; Ohmiya, Y; Maki, S; Niwa, H; Ohashi, M
Bull. Chem. Soc. Jpn., 73, 2, pp. 465-469, 2000, Peer-reviwed
Scientific journal, English

Differentiation Between N-Acetylchondrosine and N-Acetyldermosin by Matrix-assisted Laser Desorption Ionization Time-of-flight Post Source Decay Mass Spectrometry.
Mamoru Ohashi; Masami Araki; Takumi Saisu; Takuji Nabetani; Haruki Niwa
J. Mass Spectrom. Jpn., 48, 1, pp. 26-31, 2000, Peer-reviwed
Scientific journal, English

Phosphopeptide sequencing by in-source decay spectrum in delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry
T Kinumi; H Niwa; H Matsumoto
ANALYTICAL BIOCHEMISTRY, ACADEMIC PRESS INC, 277, 2, 177-186, Jan. 2000, Peer-reviwed, Protein phosphorylation underlies numerous cellular signaling processes. Since a reliable prediction of phosphorylation site(s) based on a consensus amino acid sequence is rather difficult to date, determination of phosphorylation site(s) in phosphoproteins is a crucial step toward the understanding of their function at the molecular level. A conventional protocol for the determination of phosphorylation sites utilizes radioactive labeling of a phosphoprotein by P-32 and purification of digested peptides carrying radioactivity, followed by Edman degradation. This method is not only tedious, but also indirect because the evidence will be based on disappearance of a phenylthiohydantoin signal from the degradation cycle where the P-32 radioactivity is eluted, Several methodologies have been developed to determine the phosphorylation sites directly by using mass spectrometry. These include collision-induced dissociation (CLD) and post-source decay (PSD), both of which tend to produce fragment ions less efficiently as the number of residues exceeds 20, Moreover, in both decay processes, there is a tendency for the phosphate group to be removed during the breakdown of the main peptide chain. We report a method that allows direct observation of phosphorylated peptide fragments of phosphopeptides exceeding 20 residues by using an in-source decay fragmentation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, yielding results which are difficult or impossible to obtain by existing methods using CID or PSD. (C) Academic Press.
Scientific journal, English

Selective alkene hydrogenation with atomic hydrogen permeating through a Pd sheet electrode
S Maki; Y Harada; T Hirano; H Niwa; Y Yoshida; S Ogata; S Nakamatsu; H Inoue; C Iwakura
SYNTHETIC COMMUNICATIONS, TAYLOR & FRANCIS INC, 30, 19, 3575-3583, 2000, Peer-reviwed, Chemoselective hydrogenation of olefinic double bonds without concomitant hydrogenolysis of allylic and benzylic C-O linkages was performed successfully by the aid of active hydrogen permeated through a Pd sheet electrode.
Scientific journal, English

Purification and Chracteristic Properties of the Luciferase from the Marine Ostracod Vargula hilgendorfii.
Koji Kobayashi; Daisaku Shinohara; Takuji Nabetani; Haruki Niwa; Yoshihiro Ohmiya
ITE Letters on Batteries, New Technologies & Medicine, 1, 3, pp. 422-426, 2000, Peer-reviwed
Scientific journal, English

Reactivity and pi-facial selectivity of nucleophile addition to the radical cations of 7-benzhydrylidenenorbornene derivatives
H Ishii; S Shiina; T Hirano; H Niwa; M Ohashi
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 40, 3, 523-526, Jan. 1999, Peer-reviwed, For correlating a homoconjugation structure of a radical cation to its reactivity with a nucleophile, the reactivity and pi-facial selectivity of CH3OH and H2O addition to the radical cations of 7-benzhydrylidenenorbornene derivatives generated by photoinduced electron transfer reactions were investigated. (C) 1998 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

Regiocontrolled construction of functionalized spiro[4,4]nonanones through mercury(II) salt-assisted and acid-induced spiroannulation reactions
Y Hashizume; S Maki; M Ohashi; H Niwa
SYNTHETIC COMMUNICATIONS, MARCEL DEKKER INC, 29, 7, 1223-1233, 1999, Peer-reviwed, The mercuric(II)-assisted spiroannulation reactions of the enol silyl ethers derived from alpha-(4-pentynyl)-cyclopentanones 8a and 11 gave functionalized spiro[4.4]nonanones, exo-3 and exo-4, respectively, in moderate yields. On the other hand, the treatment of 8a and 8b with methanesulfonic acid provided endo-3 in high yield.
Scientific journal, English

Stereoselective tandem cyclization of 1,1-diphenyl-1,n-alkadienes via photoinduced electron transfer reaction
H Ishii; R Yamaoka; Y Imai; T Hirano; S Maki; H Niwa; D Hashizume; F Iwasaki; M Ohashi
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 39, 51, 9501-9504, Dec. 1998, Peer-reviwed, The photoinduced electron transfer reaction of 1,1-diphenyl- 1,n-alkadienes in the presence of phenanthrene and 1,4-dicyanobenzene as a sensitizer and an electron acceptor, respectively gave intramolecular tandem cyclization products in highly stereocontrolled manner. (C) 1998 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

Synthesis of (+/-)-isoitalicene by electrolysis under irradiation as a key step
Y Harada; S Maki; H Niwa; T Hirano; S Yamamura
SYNLETT, GEORG THIEME VERLAG, 12, 1313-1314, Dec. 1998, Peer-reviwed, By utilizing electrolysis under irradiation, isoitalicene possessing a unique tricycle [5.4.0.0(1,5)] undec-8-ene skeleton was efficiently synthesized in high yield from a phenol derivative bearing an olefinic side chain.
Scientific journal, English

Synthesis of dimethyl gloiosiphone A
Y Hashizume; S Maki; M Ohashi; H Niwa
SYNLETT, GEORG THIEME VERLAG, 12, 1357-1358, Dec. 1998, Peer-reviwed, A formal total synthesis of dimethyl gloiosiphone A (1) possessing a novel, densely oxygenated spiro[4.4]nonanedione framework was achieved starting with 6-methylenespiro[4.4]nonan-1-one.
Scientific journal, English

Bioluminescent properties of fluorinated semi-synthetic aequorins
Takashi Hirano; Yoshihiro Ohmiya; Shojiro Maki; Haruki Niwa; Mamoru Ohashi
Tetrahedron Letters, 39, 31, 5541-5544, 30 Jul. 1998, Peer-reviwed, Bioluminescent properties of semi-synthetic aequorins containing coelenterazine analogues possessing fluoro group(s) on the 6-(4- hydroxyphenyl) group match the fluorescent behavior of the phenolate anions of the corresponding fluorinated coelenteramide analogues, indicating that the phenolate anion of coelenteramide is the light-emitter in aequorin bioluminescence.
Scientific journal, English

A novel, stereoselective photo-Ritter reaction of 1,1-diphenyl-1,6-heptadiene via photoindnced electron transfer reaction
H Ishii; T Hirano; S Maki; H Niwa; M Ohashi
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 39, 18, 2791-2792, Apr. 1998, Peer-reviwed, Irradiation of a wet acetonitrile nitrile solution of 1,1-diphenyl-1,6-heptadiene in the presence of 1,4-dicyanobenzene and phenanthrene provided cis-1-acetamido-3-(diphenylmethyl)cyclohexane in high yields with high stereoselectivity. Several examples leading to cis-1-acylamino-3-(diphenylmethyl)cyclohexanes were also described. (C) 1998 Elsevier Science Ltd. All rights reserved.
Scientific journal, English

"Fluorescent Properties of Model Chromophores of Tyrosine-66 Substituted Mutants of Aequorea Green Fluorescent Protein(GFP)"
Satoshi Kojima; Hiroko Ohkawa; Takashi Hirono; Haruki Niwa; Mamoru Ohashi; satoshi Inouye; Frederick I. Tsuji
Tetrahedron Letters, Elsevier Ltd., 39, 29, 5239-5242, 1998, Peer-reviwed, GFPの発色団は６５−６７番目のSer-Tyr-Glyの間で形成する．近年，異なる蛍光性を示すGFP変異体GFP Y66F，GFP Y66Hなどが作製されているがその発色団構造に関する知見はない．本報告では各変異体に対応する発色団のモデル化合物を合成しその蛍光挙動を検討した．また，各変異体タンパクを発現させその蛍光スペクトルよりモデル化合物の構造の妥当性を明らかとした．
Scientific journal, English

Substituent effects on the chemiluminescent properties of coelenterazine analogues
R Saito; T Hirano; H Niwa; M Ohashi
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 27, 1, 95-96, 1998, Peer-reviwed, Chemiluminescence maxima and quantum yields sf coelenterazine analogues possessing a substituent R [= CF3, F, H, OCH3, OH, N(CH3)(2)] at the para-position on the 6-phenyl group were measured in DMSO, The result indicates that the variation of the electronic properties of R of these analogues caused the small change of the efficiency of chemical generation of a singlet excited light-emitter (Phi(S)).
Scientific journal, English

FAB-CID Mass Spectrometry of Imizdazplone DErivatives Related to the Chromophore of Green Fluorescent Potein in Jellyfish Bioluminescence.
Toshikazu Hiraki; Masayasu Kubota; Takashi Hirano; Haruki Niwa; Mamoru Ohashi
J. Mass Spectrom. Jpn., 46, 1, pp. 37-43, 1998, Peer-reviwed
Scientific journal, English

Fluorescent Properties of Model Chromophores for the Mutant Proteins of Aequorea Green Fluorescent Protein(GFP).
Satoshi Kojima; Hiroko Ohkawa; Takashi Hirono; Haruki Niwa; Mamoru Ohashi; satoshi Inouye; Frederick I. Tsuji
Tetrahedron Lett., 39, 29, pp. 5239-5243, 1998, Peer-reviwed
Scientific journal, English

Bioluminescent Properties of Fluorinated Semi-synthetic Aequorins : Structure Elucidation of the Light-emitter in Aequorin Bioluminescence.
Takashi Hirano; Yoshihiro Ohmiya; Shojiro Maki; Haruki Niwa; Mamoru Ohashi
Tetrahedron Lett., 39, 31, pp. 5541-5545, 1998, Peer-reviwed
Scientific journal, English

FAB CID-MS/MS of In-source Fragment Ions as a Means to Differenciate Linkage Isomers of Branched Sugars : Le＾a＾ and Le＾x ＾Type Glycoconjugates.
Yoko Ohashi; Tadashi Ii; Masayasu Kubota; Shigeki Nunomura; Haruki Niwa; Mamoru Ohashi; Tomoyo Ogawa; Yoshitaka Nagai
J. Mass Spectrom. Jpn., The Mass Spectrometry Society of Japan, 46, 1, pp. 45-52, 1998, Peer-reviwed, Here we report that FAB CID-MS/MS, choosing an ion originating from the in-source degradation prior to the full acceleration of the molecule-related ion as the precursor, is an excellent means to differentiate linkage isomers. FAB CID-MS/MS performed in this way results in a product ion spectrum, which is enriched with the fragmentation information, and which may thus indicate the position of the newly formed OH group already produced in the ion source. Linkage knowledge may be classified into one of three categories as described later. This method was applied to acidic Lewis-type glycoconjugates —putative ligands for selectins [L. L. W. Cooling, D.-S. Zhang, and T. A. W. Koerner, Trends in Glycosci. Glycotech., 9, 191 (1997)]— and their neutral analogs to differentiate linkage isomers by mass spectrometry. With these glycoconjugates FAB CID-MS/MS having [M+H]⁺s as the precursor ions is a good means to distinguish the linkage isomers only in simple cases, but not in general cases. By using ions originating from in-source degradation prior to the full acceleration of the molecule-related ion as the precursor, we were able to differentiate between Le^a and Le^x.
Scientific journal, English

Novel dehydration reaction of neoanisatin and transformation of neoanisatin into anisatin
J Yoshizawa; K Obitsu; S Maki; H Niwa; T Hirano; M Ohashi
SYNLETT, GEORG THIEME VERLAG, 12, 1387-1388, Dec. 1997, Peer-reviwed, Reaction of neoanisatin with methyl oxalyl chloride in pyridine gave a novel dehydration product, from which anisatin was prepared.
Scientific journal, English

Facile cleavage reactions of styrylic olefins using electrochemical methods
S Maki; H Niwa; T Hirano
SYNLETT, GEORG THIEME VERLAG, 12, 1385-1386, Dec. 1997, Peer-reviwed, Negative constant current electrolysis of styrylic olefins in an aqueous solvent resulted in the oxidative cleavage of the double bonds, giving carbonyl compounds in good yields. The double bond conjugated with more than one aromatic ring was selectively cleaved.
Scientific journal, English

An efficient synthesis of racemic necine bases from a common intermediate
H Niwa; A Kuroda; T Sakata; K Yamada
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 70, 10, 2541-2543, Oct. 1997, Peer-reviwed, Necine bases of pyrrolizidine alkaloids, turneforcidine, hastanecine, and platynecine are synthesized from ethyl 1-hydroxy-2,3,5,6-tetrahydro-1H-pyrrolizine-7-carboxylate in racemic form.
Scientific journal, English

Solvent and substituent effects on the fluorescent properties of coelenteramide analogues
R Saito; T Hirano; H Niwa; M Ohashi
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2, ROYAL SOC CHEMISTRY, 9, 1711-1716, Sep. 1997, Peer-reviwed, Coelenteramide 1 is the light emitter in aequorin bioluminescence. To establish the fluorescent character of 1, the fluorescence properties of 1 and a series of its analogues, 3a-f, possessing a substituent R [= CF3, F, H, OCH3, OH, N(CH3)(2)] at the para-position on the 5-phenyl group have been investigated in solvents of various polarity. The fluorescence emission maxima of 1 and 3d-f, possessing an electron-donating group R [= OCH3, OH, N(CH3)(2)] shift to lower energy with increasing solvent polarity, while those of the analogues 3a-c (R = CF3, F, H) are independent of the solvent polarity. The linear correlation between the fluorescence maxima of 1 and 3d-f and the solvent polarity scales can be explained by formation of the singlet excited state with a charge-transfer (CT) character. The quantum yields of CT fluorescence of 1 and 3d-f have been found to be higher than those of 3a-c. These results indicate that the solvatochromic fluorescence of 1 originates from the CT excited state and the existence of an electron donating hydroxy group on the 5-phenyl group is essential for determining a wavelength and a high fluorescence quantum yield of aequorin bioluminescence.
Scientific journal, English

Abnormal reactivity of anisatin and neoanisatin to samarium iodide hexamethylphosphorictriamide
K Obitsu; S Maki; H Niwa; T Hirano; M Ohashi
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 38, 23, 4111-4112, Jun. 1997, Peer-reviwed, Reactions of anisatin and neoanisatin with SmI2 in the presence of HMPA give novel products having an oxaadamanthane skeleton accompanied by decarboxylation from the spiro beta-lactone functionality. (C) 1997 Elsevier Science Ltd.
Scientific journal, English

Mechanism of the redox reaction of the Aequorea green fluorescent protein (GFP)
S Kojima; T Hirano; H Niwa; M Ohashi; S Inouye; FL Tsuji
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 38, 16, 2875-2878, Apr. 1997, Peer-reviwed, A model compound, 4-(4-hydroxyphenyl)methylideneimidazol-5-one undergoes a reversible redox reaction identical to that of the Aequorea green fluorescent protein (GFP), strongly suggesting that the GFP chromophore is derived via the autoxidation of a nonfluorescent dihydro precursor in dihydro-GFP. (C) 1997 Elsevier Science Ltd.
Scientific journal, English

Aequorea green fluorescent protein: Structural elucidation of the chromophore
H Niwa; T Matsuno; S Kojima; M Kubota; T Hirano; M Ohashi; S Inouye; Y Ohmiya; FI Tsuji
BIOLUMINESCENCE AND CHEMILUMINESCENCE, JOHN WILEY & SONS LTD, 395-398, 1997, Peer-reviwed
International conference proceedings, English

Chemical nature of the light emitter of the Aequorea green fluorescent protein
H Niwa; S Inouye; T Hirano; T Matsuno; S Kojima; M Kubota; M Ohashi; FI Tsuji
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, NATL ACAD SCIENCES, 93, 24, 13617-13622, Nov. 1996, Peer-reviwed, The jellyfish Aequorea victoria possesses in the margin of its umbrella a green fluorescent protein (GFP, 27 kDa) that serves as the ultimate light emitter in the bioluminescence reaction of the animal, The protein is made up of 238 amino acid residues in a single polypeptide chain and produces a greenish fluorescence (lambda(max) = 508 nm) when irradiated with long ultraviolet light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide -Ser(65)-Tyr(66)-Gly(67)-. GFP has been used extensively as a reporter protein for monitoring gene expression in eukaryotic and prokaryotic cells, but relatively little is known about the chemical mechanism by which fluorescence is produced, To obtain a better understanding of this problem, we studied a peptide fragment of GFP bearing the chromophore and a synthetic model compound of the chromophore, The results indicate that the GFP chromophore consists of an imidazolone ring structure and that the light emitter is the singlet excited state of the phenolate anion of the chromophore, Further, the light emission is highly dependent on the microenvironment around the chromophore and that inhibition of isomerization of the exo-methylene double bond of the chromophore accounts for its efficient light emission.
Scientific journal, English

Unusual reactions of C-60 with aldehydes in the presence of aqueous ammonia
A Komori; M Kubota; T Ishida; H Niwa; T Nogami
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 37, 23, 4031-4034, Jun. 1996, Peer-reviwed, Fullerene C-60 reacts with alkylaldehydes in the presence of aqueous ammonia to give 2,5-dialkyl-substituted pyrrolidine derivatives. The reaction of phenylacetaldehyde under similar conditions afforded C-60(H)(CH(2)Ph) via possible decarbonylation. On the basis of the product analysis, reaction mechanisms are proposed in which C-60 plays the role of a dipolarophile or radical scavenger. (C) 1996 Elsevier Science Ltd.
Scientific journal, English

A POTENTIAL PHOTOAFFINITY PROBE FOR LABELING THE ACTIVE-SITE OF AEQUORIN - A PHOTOLABILE COELENTERAZINE ANALOG WITH A TRIFLUOROMETHYLDIAZIRINE GROUP
FQ CHEN; JL ZHENG; T HIRANO; H NIWA; Y OHMIYA; M OHASHI
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, ROYAL SOC CHEMISTRY, 17, 2129-2134, Sep. 1995, Peer-reviwed, In order to clarify the active site of aequorin, we have: successfully synthesized a photolabile analogue of coelenterazine with a trifluoromethyldiazirine group as a photoaffinity probe. Our studies on the chemi- and bio-luminescence of this novel analogue indicate that its behaviour is almost identical with that of natural coelenterazine in terms of luminescence characteristics. Therefore, the analogue with the photolabile diazirine should be a useful photoaffinity label for probing the detailed structure of aequorin.
Scientific journal, English

ENANTIOSELECTIVE SYNTHESIS OF THE MACROCYCLIC PYRROLIZIDINE ALKALOID YAMATAIMINE
H NIWA; K KUNITANI; T NAGOYA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 67, 11, 3094-3099, Nov. 1994, Peer-reviwed, Described is a short-step synthesis of optically active yamataimine, a 12-membered pyrrolizidine alkaloid of retronecine type. Methyl (1S,SR)-5-methyl-2-oxocyclopentanecarboxylate derived from (R)-(+)-pulegone was converted into the necic acid component required for the synthesis of yamataimine, in a nine-step sequence. Regioselective coupling of (+)-retronecine with the necic acid component via tin-mediated regioselective acylation followed by macrolactonization led to the first synthesis of (+)-yamataimine.
Scientific journal, English

AN IMPROVED SYNTHESIS OF (+/-)-OTONECINE AND A SYNTHESIS OF A 12-MEMBERED OTONECINE DIESTER
H NIWA; T SAKATA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 67, 8, 2345-2347, Aug. 1994, Peer-reviwed, (+/-)-4-Methyl-1-phenylthio-8-oxa-4-azabicyclo[5.2.1]decane-9,10-dione was efficiently converted into (+/-)-otonecine, which was regioselectively coupled with (E)-2-ethylidenehexanedioic acid to give a 12-membered otonecine diester.
Scientific journal, English

A SYNTHESIS OF SENECIONINE, A REPRESENTATIVE OF HEPATOTOXIC, MACROCYCLIC PYRROLIZIDINE ALKALOIDS OF RETRONECINE TYPE
H NIWA; T SAKATA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 67, 7, 1990-1993, Jul. 1994, Peer-reviwed, Described is a synthesis of (-)-senecionine, the best-known hepatotoxic, 12-membered pyrrolizidine alkaloid of retronecine type. Integerrinecic acid lactone methyl ester was converted into protected senecic acid, which was regioselectively coupled with (+)-retronecine, achieving the first synthesis of (-)-senecionine.
Scientific journal, English

DIDEMNILACTONE-A AND DIDEMNILACTONE-B AND NEODIDEMNILACTONE, 3 NEW FATTY-ACID METABOLITES ISOLATED FROM THE TUNICATE DIDEMNUM MOSELEYI (HERDMAN)
H NIWA; M WATANABE; H INAGAKI; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 50, 25, 7385-7400, Jun. 1994, Peer-reviwed, Three new fatty acid metabolites didemnilactones A (1) and B (2) and neodidemnilactone (3) were isolated from the tunicate Didemnum moseleyi (Herdman). Their structures including absolute stereochemistry were established on the basis of spectral studies and chemical synthesis. Didemnilactones exhibited inhibitory activity against lipoxygenase and weak binding activity to leukotriene B-4 receptors.
Scientific journal, English

Structures of monodontamides A, B, C, D, E, and F, six new alkaloids isolated from the marine gastropod mollusc Monodonta labio (Linné)
Haruki Niwa; Masaru Watanabe; Atsushi Sano; Kiyoyuki Yamada
Tetrahedron, 50, 23, 6805-6818, 1994, Peer-reviwed, Six new alkaloids monodontamides A (1), B (2), C (3), D (4), E (5), and F (6) were isolated from the marine gastropod mollusc Monodonta labio (Linné). The structures of monodontamides were established on the basis of spectral data and unambiguous synthesis. Monodontamides exhibited weak inhibitory activity against a serine protease. © 1994.
Scientific journal, English

Monodontamides A, B, and C, three new putrescine alkaloids from the marine gastropod mollusc Monodonta labio (Linné)
Haruki Niwa; Masaru Watanabe; Kiyoyuki Yamada
Tetrahedron Letters, 34, 46, 7441-7444, 12 Nov. 1993, Peer-reviwed, Described are the structure determination and synthesis of three new alkaloids, monodontamides A (1), B (2), and C (3) isolated from the marine gastropod mollusc Monodonta labio (Linné). © 1993.
Scientific journal, English

TOTAL SYNTHESIS OF NATURAL (-)-PTAQUILOSIN, THE AGLYCON OF A POTENT BRACKEN CARCINOGEN PTAQUILOSIDE, AND THE (+)-ENANTIOMER AND THEIR DNA CLEAVING ACTIVITIES
H KIGOSHI; Y IMAMURA; K MIZUTA; H NIWA; K YAMADA
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMER CHEMICAL SOC, 115, 8, 3056-3065, Apr. 1993, Peer-reviwed, The total synthesis of natural (-)-ptaquilosin (2) the aglycon of a potent carcinogen ptaquiloside (1) from bracken fern and its (+)-enantiomer (2) has been achieved starting with (+)-dimenthyl (1R,2R)-cyclopentane-1,2-dicarboxylate. The synthesis proceeds in 20 steps (2.9% overall yield). The key features of the synthesis are as follows: (i) diastereoselective alkylation of a common chiral compound 5 under different conditions has provided each of two diastereomers 6a and 6b predominantly, the former 6a eventually leading to natural (-)-2 and the latter 6b giving unnatural (+)-2 and (ii) the deformylative oxidation reaction of aldehyde 23 has been effected under the conditions mild enough to permit survival of the unstable product ptaquilosin (2). As to the DNA cleaving activities, dienone 4 prepared from natural (-)-ptaquilosin (2) was shown to be more efficient than dienone 4 derived from unnatural (+)-ptaquilosin (2).
Scientific journal, English

AN EFFICIENT ENANTIOSELECTIVE SYNTHESIS OF INDICINE N-OXIDE, AN ANTITUMOR PYRROLIZIDINE ALKALOID
T OGAWA; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 49, 8, 1571-1578, Feb. 1993, Peer-reviwed, Indicine N-oxide (1), a pyrrolizidine alkaloid potentially useful for an anticancer drug was synthesized in the natural form through regioselective coupling of (+)-retronecine (2) and the protected necic acids 16a and 16b, the latter being efficiently prepared from the optically pure lactone 5.
Scientific journal, English

TOTAL SYNTHESIS OF OPTICALLY-ACTIVE MONOCROTALINE, A CARCINOGENIC PYRROLIZIDINE ALKALOID POSSESSING AN 11-MEMBERED RETRONECINE DILACTONE
H NIWA; T OGAWA; O OKAMOTO; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 48, 48, 10531-10548, Nov. 1992, Peer-reviwed, A total synthesis of the natural enantiomer of monocrotaline (1), a representative of carcinogenic pyrrolizidine alkaloids having an 11-membered retronecine dilactone was achieved through regioselective coupling of (+)-retronecine (3) and the optically active protected necic acid 8, the latter being prepared enantioselectively from the meso-diester 11.
Scientific journal, English

TOTAL SYNTHESIS OF OPTICALLY-ACTIVE INTEGERRIMINE, A 12-MEMBERED DILACTONIC PYRROLIZIDINE ALKALOID OF RETRONECINE TYPE
H NIWA; Y MIYACHI; O OKAMOTO; Y UOSAKI; A KURODA; H ISHIWATA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 48, 3, 393-412, Jan. 1992, Peer-reviwed, A total synthesis of the natural enantiomer of integerrimine (1), a twelve-membered dilactonic pyrrolizidine alkaloid of retronccine type has been achieved through the enantioselective synthesis and regioselective coupling of (+)-retronecine (4) and (+)-integerrinecic acid (methylthio)methyl ether (6).
Scientific journal, English

NOVEL TRANSFORMATION OF FORMYL GROUPS INTO HYDROXYL-GROUPS UTILIZING DEFORMYLATIVE AUTOXIDATION OF ALDEHYDES
H KIGOSHI; Y IMAMURA; A SAWADA; H NIWA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 64, 12, 3735-3737, Dec. 1991, Peer-reviwed, Structural requirements that cause deformylative autoxidation of aliphatic aldehydes are investigated. Decarbonylation of acyl radicals proceeds smoothly when the alkyl radicals that are formed can be stabilized by allylic conjugation. Further conjugation of the double bond in the allyl radical with a carbonyl or a cyclopropyl group allows position-selective peroxidation of the alkyl radical.
Scientific journal, English

FURTHER CHEMICAL STUDIES ON ANISATIN, A NEUROTOXIC SESQUITERPENOID HAVING A BETA-LACTONE
H NIWA; TSUKADA, I; M NISIWAKI; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 64, 9, 2860-2862, Sep. 1991, Peer-reviwed, By a series of chemical reactions, anisatin was efficiently converted into the key intermediate employed in the synthesis of anisatin.
Scientific journal, English

DIDEMNILACTONE AND NEODIDEMNILACTONE, 2 NEW FATTY-ACID METABOLITES POSSESSING A 10-MEMBERED LACTONE FROM THE TUNICATE DIDEMNUM-MOSELEYI (HERDMAN)
H NIWA; H INAGAKI; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 32, 38, 5127-5128, Sep. 1991, Peer-reviwed, Didemnilactone (1) and neodidemnilactone (2), two new fatty acid metabolites possessing a 10-membered lactone were isolated from the colonial tunicate Didemnum moseleyi (Herdman). Their structures including absolute stereochemistry were determined on the basis of spectral studies and the enantioselective synthesis of the antipode of 2.
Scientific journal, English

FACTORS THAT CAUSE CONTRASTERIC ALKYLATION OF A CYCLOPENTANE-1,2-DICARBOXYLIC ACID MONOESTER
H KIGOSHI; Y IMAMURA; K YOSHIKAWA; H NIWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 32, 35, 4541-4544, Aug. 1991, Peer-reviwed, The stereochemical outcome in the alkylation of the enolate generated from a cyclopentane-1,2-dicarboxylic acid monoester is described. The alkylation of the Li enolate with an alkylating reagent having a hard leaving group such as Cl gave a contrasteric alkylation (alkylation from the more hindered side of the enolate) product, predominantly. An important factor effecting contrasteric alkylation was found to be complexation of the hard leaving group of the alkylating reagent to the carboxylate Li counterion in the enolate.
Scientific journal, English

THE 3-DIMENSIONAL STRUCTURE OF NEOHALICHOLACTONE, AN UNUSUAL FATTY-ACID METABOLITE FROM THE MARINE SPONGE HALICHONDRIA-OKADAI KADOTA
H KIGOSHI; H NIWA; K YAMADA; TJ STOUT; J CLARDY
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 32, 22, 2427-2428, May 1991, Peer-reviwed, The three-dimensional structure of the unusual fatty acid metabolite neohalicholactone, isolated from the marine sponge Halichondria okadai Kadota, has been determined by X-ray crystallography.
Scientific journal, English

SYNTHESIS OF (-)-NEOANISATIN, A NEUROTOXIC SESQUITERPENOID HAVING A NOVEL SPIRO BETA-LACTONE
H NIWA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 20, 4, 639-640, Apr. 1991, Peer-reviwed, (-)-Anisatin can be converted into (-)-neoanisatin, which accomplishes the total synthesis of the natural enantiomer of neoanisatin.
Scientific journal, English

SYNTHESIS OF (-)-NORANISATIN, AN OXIDATION-PRODUCT OF A NEUROTOXIC SESQUITERPENOID ANISATIN HAVING A NOVEL SPIRO BETA-LACTONE
H NIWA; S ITO; T HASEGAWA; K WAKAMATSU; T MORI; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 32, 10, 1329-1330, Mar. 1991, Peer-reviwed, The synthesis of (-)-noranisatin (2), an oxidation product of anisatin (1) possessing a novel spiro beta-lactone, was achieved starting from triol 5 prepared from (R)-(+)-pulegone (3).
Scientific journal, English

TOTAL SYNTHESIS OF (+/-)-(Z)-9-(BROMOMETHYLENE)-1,5,5-TRIMETHYLSPIRO[5.5]UNDECA-1,7-DIEN-3-ONE, A BROMINATED SESQUITERPENE OF THE CHAMIGRANE TYPE
H NIWA; Y YOSHIDA; T HASEGAWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 47, 12-13, 2155-2162, Mar. 1991, Peer-reviwed, (+/-)-(Z)-9-(Bromomethylene)-1,5,5-trimethylspirol[5.5]undeca-1,7-dien-3-one (1), a chamigrane sesquiterpene having a novel bromomethylene group is synthesized from anisole via spiroannelation of 4-(1,1-dimethyl-4-formylbutyl)-3-cyclohexen-1-one (10).
Scientific journal, English

ALKYLATION OF NUCLEOSIDES BY DEHYDROMONOCROTALINE, THE PUTATIVE TOXIC METABOLITE OF THE CARCINOGENIC PYRROLIZIDINE ALKALOID MONOCROTALINE
H NIWA; T OGAWA; O OKAMOTO; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 32, 7, 927-930, Feb. 1991, Peer-reviwed, Reaction of dehydromonocrotaline (3), the putative toxic metabolite of the carcinogenic pyrrolizidine alkaloid monocrotaline (2), with various nucleosides proceeded mostly at the C-9'' position of 3 to give several nitrogen atom-alkylated nucleosides including N-7 alkylated 2'-deoxyguanosine 14.
Scientific journal, English

ON THE MECHANISM OF THE CLEAVAGE REACTION OF (METHYLTHIO)METHYL ETHER WITH TRIPHENYLMETHYL CATION
H NIWA; Y MIYACHI
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 64, 2, 716-718, Feb. 1991, Peer-reviwed, The cleavage reaction of a (methylthio)methyl (MTM) ether with triphenylmethyl cation was not initiated by the previously proposed hydride abstraction with triphenylmethyl cation but promoted by the coordination of triphenylmethyl cation as a Lewis acid to the sulfur atom in the MTM group.
Scientific journal, English

STEREOSELECTIVE SYNTHESIS OF (-)-TRACHELANTHIC ACID AND (+)-VIRIDIFLORIC ACID, NECIC ACID COMPONENTS OF PYRROLIZIDINE ALKALOIDS FROM A COMMON INTERMEDIATE
H NIWA; T OGAWA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 63, 12, 3707-3709, Dec. 1990, Peer-reviwed, Diastereoselective reduction of a side-chain keto group in (2S,5R)-5-acetyl-2-(t-butyl)-5-isopropyl-1,3-dioxolan-4-one (5) with (i-Bu)2A1H in ether afforded (1'S,2S,5R)-2-(t-butyl)-5-(1'-hydroxyethyl)-5-isopropyl-1,3-dioxolan-4-one (6), while reduction of 5 with LiBH(s-Bu)3 in ether gave the (1'R)-isomer 7 predominantly. (-)-Trachelanthic acid (1) and (+)-viridifloric acid (2) were synthesized upon hydrolysis of 6 and 7, respectively.
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (-)-ANISATIN - A NEUROTOXIC SESQUITERPENOID POSSESSING A NOVEL SPIRO BETA-LACTONE
H NIWA; M NISIWAKI; TSUKADA, I; T ISHIGAKI; S ITO; K WAKAMATSU; T MORI; M IKAGAWA; K YAMADA
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMER CHEMICAL SOC, 112, 24, 9001-9003, Nov. 1990, Peer-reviwed
Scientific journal, English

A BIOGENETIC-TYPE SYNTHESIS OF (+/-)-APLYSIADIOL, A BROMINATED DITERPENE ISOLATED FROM THE MARINE MOLLUSK APLYSIA-KURODAI
H NIWA; S IEDA; H INAGAKI; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 31, 49, 7157-7158, 1990, Peer-reviwed
Scientific journal, English

ACUTE MICROCIRCULATORY CHANGES INDUCED BY INTRAVENOUS ADMINISTRATION TO RABBITS OF PTAQUILOSIDE, A BRACKEN CARCINOGEN
M ASANO; C OHKUBO; A SASAKI; HIRONO, I; K YAMADA; H NIWA; M OJIKA
JOURNAL OF ETHNOPHARMACOLOGY, ELSEVIER SCI IRELAND LTD, 27, 1-2, 213-220, Nov. 1989, Peer-reviwed
Scientific journal, English

SYNTHESIS OF A FUNCTIONALIZED CARBOCYCLIC SKELETON OF PTAQUILOSIN, THE AGLYCONE OF A BRACKEN CARCINOGEN PTAQUILOSIDE BASED ON AN INTRAMOLECULAR DIELS-ALDER REACTION
H KIGOSHI; A SAWADA; H NIWA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 62, 5, 1639-1642, May 1989, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF PTAQUILOSIN - THE AGLYCON OF PTAQUILOSIDE, A POTENT BRACKEN CARCINOGEN
H KIGOSHI; Y IMAMURA; H NIWA; K YAMADA
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMER CHEMICAL SOC, 111, 6, 2302-2303, Mar. 1989, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (+/-)-PTAQUILOSIN - THE AGLYCONE OF PTAQUILOSIDE - A BRACKEN CARCINOGEN
H KIGOSHI; A SAWADA; Y NAKAYAMA; H NIWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 30, 15, 1983-1986, 1989, Peer-reviwed
Scientific journal, English

PTAQUILOSIN, THE AGLYCONE OF A BRACKEN CARCINOGEN PTAQUILOSIDE - CHEMICAL DERIVATION FROM PTAQUILOSIDE AND THE REACTIVITY
H KIGOSHI; A SAWADA; Y IMAMURA; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 45, 9, 2551-2556, 1989, Peer-reviwed
Scientific journal, English

HALICHOLACTONE AND NEOHALICHOLACTONE, 2 NOVEL FATTY-ACID METABOLITES FROM THE MARINE SPONGE HALICHONDRIA-OKADAI KADOTA
H NIWA; K WAKAMATSU; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 30, 34, 4543-4546, 1989, Peer-reviwed
Scientific journal, English

AN EFFICIENT ENANTIOSELECTIVE SYNTHESIS OF (+)-INDICINE N-OXIDE, AN ANTITUMOR PYRROLIZIDINE ALKALOID
H NIWA; T OGAWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 30, 37, 4985-4986, 1989, Peer-reviwed
Scientific journal, English

A TIN-MEDIATED ONE-STEP SYNTHESIS OF (+)-DICROTALINE, AN 11-MEMBERED DILACTONIC PYRROLIZIDINE ALKALOID
H NIWA; O OKAMOTO; H ISHIWATA; A KURODA; Y UOSAKI; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 61, 8, 3017-3019, Aug. 1988, Peer-reviwed
Scientific journal, English

A BROMINATED QUINAZOLINEDIONE FROM THE MARINE TUNICATE PYURA-SACCIFORMIS
H NIWA; Y YOSHIDA; K YAMADA
JOURNAL OF NATURAL PRODUCTS, AMER SOC PHARMACOGNOSY, 51, 2, 343-344, Mar. 1988, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF OPTICALLY-ACTIVE MONOCROTALINE, A CARCINOGENIC PYRROLIZIDINE ALKALOID HAVING AN 11-MEMBERED DILACTONE
H NIWA; O OKAMOTO; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 29, 40, 5139-5142, 1988, Peer-reviwed
Scientific journal, English

AN EFFICIENT ENANTIOSELECTIVE SYNTHESIS OF THE (-)-N-(ETHOXYCARBONYL)METHYL GEISSMAN-WAISS LACTONE - A PRACTICAL SYNTHETIC ROUTE TO (+)-RETRONECINE
H NIWA; O OKAMOTO; Y MIYACHI; Y UOSAKI; K YAMADA
JOURNAL OF ORGANIC CHEMISTRY, AMER CHEMICAL SOC, 52, 13, 2941-2943, Jun. 1987, Peer-reviwed
Scientific journal, English

ISOLATION OF THE STRAINED BRIDGEHEAD ENOL ETHER OF A BICYCLO[3.3.1]NONAN-2-ONE SYSTEM
K WAKAMATSU; H TAN; N BAN; N UCHIYAMA; H NIWA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 16, 1, 121-122, 1987, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (+/-)-NORPATCHOULENOL AND 2 METABOLITES OF PATCHOULI ALCOHOL, (+/-)-HYDROXY PATCHOULI ALCOHOL AND THE CORRESPONDING (+/-)-CARBOXYLIC ACID
H NIWA; T HASEGAWA; N BAN; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 43, 5, 825-834, 1987, Peer-reviwed
Scientific journal, English

PTAQUILOSIDE, A POTENT CARCINOGEN ISOLATED FROM BRACKEN FERN PTERIDIUM-AQUILINUM VAR LATIUSCULUM - STRUCTURE ELUCIDATION BASED ON CHEMICAL AND SPECTRAL EVIDENCE, AND REACTIONS WITH AMINO-ACIDS, NUCLEOSIDES, AND NUCLEOTIDES
M OJIKA; K WAKAMATSU; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 43, 22, 5261-5274, 1987, Peer-reviwed
Scientific journal, English

STRUCTURES OF NEW P-HYDROXYSTYRENE GLYCOSIDES, PTELATOSIDE-A AND PTELATOSIDE-B ISOLATED FROM BRACKEN FERN, PTERIDIUM-AQUILINUM VAR LATIUSCULUM, AND SYNTHESIS OF PTELATOSIDE-A
M OJIKA; K WAKAMATSU; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 43, 22, 5275-5280, 1987, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED SYNTHESIS OF POLYFUNCTIONALIZED TRANS-HYDRINDAN SYSTEMS - A MODEL STUDY TOWARD ANISATIN
H NIWA; T MORI; T HASEGAWA; K YAMADA
JOURNAL OF ORGANIC CHEMISTRY, AMER CHEMICAL SOC, 51, 7, 1015-1018, Apr. 1986, Peer-reviwed
Scientific journal, English

4 NEW C-15 ACETYLENIC POLYENES OF BIOGENETIC SIGNIFICANCE FROM THE RED ALGA LAURENCIA-OKAMURAI - STRUCTURES AND SYNTHESIS
H KIGOSHI; Y SHIZURI; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 42, 14, 3781-3787, 1986, Peer-reviwed
Scientific journal, English

ISOLATION OF (10R,11R)-(+)-SQUALENE-10,11-EPOXIDE FROM THE RED ALGA LAURENCIA-OKAMURAI AND ITS ENANTIOSELECTIVE SYNTHESIS
H KIGOSHI; M OJIKA; Y SHIZURI; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 42, 14, 3789-3792, 1986, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF OPTICALLY-ACTIVE INTEGERRIME, A 12-MEMBERED DILACTONIC PYRROLIZIDINE ALKALOID OF RETRONECINE TYPE .1. ENANTIOSELECTIVE SYNTHESIS OF THE PROTECTED (+/-)-INTEGERRINECIC ACID
H NIWA; Y MIYACHI; Y UOSAKI; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 27, 38, 4601-4604, 1986, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF OPTICALLY-ACTIVE INTEGERRIMINE, A 12-MEMBERED DILACTONIC PYRROLIZIDINE ALKALOID OF RETRONECINE TYPE .2. ENANTIOSELECTIVE SYNTHESIS OF (+)-RETRONECINE
H NIWA; Y MIYACHI; O OKAMOTO; Y UOSAKI; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 27, 38, 4605-4608, 1986, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF OPTICALLY-ACTIVE INTEGERRIMINE, A 12-MEMBERED DILACTONIC PYRROLIZIDINE ALKALOID OF RETRONECINE TYPE .3. REGIOSELECTIVE ELABORATION OF THE UNSYMMETRICAL 12-MEMBERED DILACTONE AND TOTAL SYNTHESIS OF (-)-INTEGERRIMINE
H NIWA; Y MIYACHI; Y UOSAKI; A KURODA; H ISHIWATA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 27, 38, 4609-4610, 1986, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (+)-TUTIN AND (+)-ASTEROMURIN-A, TOXIC PICROTOXANE SESQUITERPENES
K WAKAMATSU; H KIGOSHI; K NIIYAMA; H NIWA; K YAMADA
TETRAHEDRON, PERGAMON-ELSEVIER SCIENCE LTD, 42, 20, 5551-5558, 1986, Peer-reviwed
Scientific journal, English

ISOLATION OF PETASITENINE, A CARCINOGENIC PYRROLIZIDINE ALKALOID FROM FARFUGIUM-JAPONICUM
H NIWA; H ISHIWATA; K YAMADA
JOURNAL OF NATURAL PRODUCTS, AMER SOC PHARMACOGNOSY, 48, 6, 1003-1004, Nov. 1985, Peer-reviwed
Scientific journal, English

GENOTOXICITY OF PTAQUILOSIDE, A BRACKEN CARCINOGEN, IN THE HEPATOCYTE PRIMARY CULTURE DNA-REPAIR TEST
H MORI; S SUGIE; HIRONO, I; K YAMADA; H NIWA; M OJIKA
MUTATION RESEARCH, ELSEVIER SCIENCE BV, 143, 1-2, 75-78, 1985, Peer-reviwed
Scientific journal, English

A NEW METHOD FOR DIRECT OXIDATION OF THE METHYLENE GROUP ADJACENT TO A CYCLOPROPANE RING TO THE KETO GROUP
T HASEGAWA; H NIWA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 14, 9, 1385-1386, 1985, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF (+/-)-(Z)-9-(BROMOMETHYLENE)-1,5,5-TRIMETHYLSPIRO[5.5]UNDECA-1,7-DIEN-3-ONE, A BROMINATED SESQUITERPENE OF CHAMIGRANE TYPE
H NIWA; Y YOSHIDA; T HASEGAWA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 14, 11, 1687-1688, 1985, Peer-reviwed
Scientific journal, English

STUDIES ON PTERIDIUM-AQUILINUM VAR LATIUSCULUM .4. ISOLATION OF 3 PARA-HYDROXYSTYRENE GLYCOSIDES AND AN EFFICIENT METHOD FOR THE ISOLATION OF PTAQUILOSIDE, AN UNSTABLE BRACKEN CARCINOGEN
M OJIKA; H KIGOSHI; H KUYAMA; H NIWA; K YAMADA
JOURNAL OF NATURAL PRODUCTS, AMER SOC PHARMACOGNOSY, 48, 4, 634-637, 1985, Peer-reviwed
Scientific journal, English

ACTIONS OF PICROTOXININ AND RELATED-COMPOUNDS ON THE FROG SPINAL-CORD - THE ROLE OF A HYDROXYL-GROUP AT THE 6-POSITION IN ANTAGONIZING THE ACTIONS OF AMINO-ACIDS AND PRESYNAPTIC INHIBITION
Y KUDO; H NIWA; A TANAKA; K YAMADA
BRITISH JOURNAL OF PHARMACOLOGY, STOCKTON PRESS, 81, 2, 373-380, 1984, Peer-reviwed
Scientific journal, English

SEPARATION OF CARCINOGENIC FRACTION OF BRACKEN FERN
HIRONO, I; K YAMADA; H NIWA; Y SHIZURI; M OJIKA; S HOSAKA; T YAMAJI; K WAKAMATSU; H KIGOSHI; K NIIYAMA; Y UOSAKI
CANCER LETTERS, ELSEVIER SCI IRELAND LTD, 21, 3, 239-246, 1984, Peer-reviwed
Scientific journal, English

ISOLATION AND STRUCTURES OF 2 NEW PARA-HYDROXYSTYRENE GLYCOSIDES, PTELATOSIDE-A AND PTELATOSIDE-B FROM BRACKEN, PTERIDIUM-AQUILINUM VAR LATIUSCULUM, AND SYNTHESIS OF PTELATOSIDE-A
M OJIKA; K WAKAMATSU; H NIWA; K YAMADA; HIRONO, I
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 13, 3, 397-400, 1984, Peer-reviwed
Scientific journal, English

HYPERPLASTIC NODULES OF THE LIVER INDUCED IN RATS FED BRACKEN DIET
HIRONO, I; S AISO; T YAMAJI; H NIWA; M OJIKA; K WAKAMATSU; K YAMADA
CANCER LETTERS, ELSEVIER SCI IRELAND LTD, 22, 2, 151-155, 1984, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (+/-)-HYDROXY PATCHOULI ALCOHOL AND THE CORRESPONDING (+/-)-CARBOXYLIC ACID, METABOLITES OF PATCHOULI ALCOHOL, AND (+/-)-NORPATCHOULENOL
H NIWA; T HASEGAWA; N BAN; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 25, 26, 2797-2800, 1984, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (-)-PICROTOXININ AND (+)-CORIAMYRTIN VIA A COMMON ISOTWISTANE INTERMEDIATE
H NIWA; K WAKAMATSU; T HIDA; K NIIYAMA; H KIGOSHI; M YAMADA; H NAGASE; M SUZUKI; K YAMADA
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMER CHEMICAL SOC, 106, 16, 4547-4552, 1984, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (+)-TUTIN, A TOXIC SESQUITERPENE OF PICROTOXANE TYPE
K WAKAMATSU; H KIGOSHI; K NIIYAMA; H NIWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 25, 35, 3873-3874, 1984, Peer-reviwed
Scientific journal, English

STEREOCONTROLLED TOTAL SYNTHESIS OF (+)-ASTEROMURIN-A, A PICROTOXANE SESQUITERPENE ISOLATED FROM THE SCALE INSECT ASTEROCOCCUS-MURATAE KUWANA
K WAKAMATSU; K NIIYAMA; H NIWA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 13, 10, 1763-1764, 1984, Peer-reviwed
Scientific journal, English

REPRODUCTION OF ACUTE BRACKEN POISONING IN A CALF WITH PTAQUILOSIDE, A BRACKEN CONSTITUENT
HIRONO, I; Y KONO; K TAKAHASHI; K YAMADA; H NIWA; M OJIKA; H KIGOSHI; K NIIYAMA; Y UOSAKI
VETERINARY RECORD, BRITISH VETERINARY ASSOC, 115, 15, 375-378, 1984, Peer-reviwed
Scientific journal, English

STRUCTURE AND SYNTHESIS OF MIYAGININ, A PARA-ALLYLPHENYL GLYCOSIDE FROM LESPEDEZA-THUNBERGII FORMA MACRANTHA
M OJIKA; H KUYAMA; H NIWA; K YAMADA
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, CHEMICAL SOC JAPAN, 57, 10, 2893-2896, 1984, Peer-reviwed
Scientific journal, English

CARCINOGENICITY IN RATS OF PTAQUILOSIDE ISOLATED FROM BRACKEN
HIRONO, I; S AISO; T YAMAJI; H MORI; K YAMADA; H NIWA; M OJIKA; K WAKAMATSU; H KIGOSHI; K NIIYAMA; Y UOSAKI
GANN, JAPAN CANCER ASSN CANCER INST, 75, 10, 833-836, 1984, Peer-reviwed
Scientific journal, English

STRUCTURE OF PTAQUILOSIDE TETRAACETATE, C28H38O12
S OHBA; Y SAITO; HIRONO, I; H NIWA; M OJIKA; K WAKAMATSU; K YAMADA
ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, MUNKSGAARD INT PUBL LTD, 40, NOV, 1877-1879, 1984, Peer-reviwed
Scientific journal, English

A CONVENIENT SYNTHESIS OF (+/-)-RETRONECINE
H NIWA; A KURODA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 12, 1, 125-126, 1983, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF (+/-)-CYCLOSEYCHELLENE, A NOVEL TETRACYCLIC SESQUITERPENE
H NIWA; N BAN; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 24, 9, 937-938, 1983, Peer-reviwed
Scientific journal, English

SEPARATION AND DETERMINATION OF MACROCYCLIC PYRROLIZIDINE ALKALOIDS OF THE OTONECINE TYPE PRESENT IN THE EDIBLE PLANT PETASITES-JAPONICUS BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY
H NIWA; H ISHIWATA; K YAMADA
JOURNAL OF CHROMATOGRAPHY, ELSEVIER SCIENCE BV, 257, 1, 146-150, 1983, Peer-reviwed
Scientific journal, English

FARFUGINE, A NEW PYRROLIZIDINE ALKALOID ISOLATED FROM FARFUGIUM-JAPONICUM KITAM
H NIWA; H ISHIWATA; A KURODA; K YAMADA
CHEMISTRY LETTERS, CHEMICAL SOC JAPAN, 12, 5, 789-790, 1983, Peer-reviwed
Scientific journal, English

PTAQUILOSIDE, A NOVEL NORSESQUITERPENE GLUCOSIDE FROM BRACKEN, PTERIDIUM-AQUILINUM VAR LATIUSCULUM
H NIWA; M OJIKA; K WAKAMATSU; K YAMADA; HIRONO, I; K MATSUSHITA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 24, 38, 4117-4120, 1983, Peer-reviwed
Scientific journal, English

STEREOCHEMISTRY OF PTAQUILOSIDE, A NOVEL NORSESQUITERPENE GLUCOSIDE FROM BRACKEN, PTERIDIUM-AQUILINUM VAR LATIUSCULUM
H NIWA; M OJIKA; K WAKAMATSU; K YAMADA; S OHBA; Y SAITO; HIRONO, I; K MATSUSHITA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 24, 48, 5371-5372, 1983, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF (+/-)-OTONECINE, A NECINE BASE OF PYRROLIZIDINE ALKALOIDS
H NIWA; Y UOSAKI; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 24, 51, 5731-5732, 1983, Peer-reviwed
Scientific journal, English

SYNTHESIS OF (+1)-CARBA-ANALOGS OF 5-HPETE AND LEUKOTRIENE A4, UNSTABLE INTERMEDIATES OF SLOW-REACTING SUBSTANCE (SRS)
Y ARAI; M KONNO; K SHIMOJI; Y KONISHI; H NIWA; M TODA; M HAYASHI
CHEMICAL & PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOC JAPAN, 30, 1, 379-382, 1982, Peer-reviwed
Scientific journal, English

STRUCTURAL ANALOGS OF LEUKOTRIENE-C AND LEUKOTRIENE-D AND THEIR CONTRACTILE ACTIVITIES
S OKUYAMA; S MIYAMOTO; K SHIMOJI; Y KONISHI; D FUKUSHIMA; H NIWA; Y ARAI; M TODA; M HAYASHI
CHEMICAL & PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOC JAPAN, 30, 7, 2453-2462, 1982, Peer-reviwed
Scientific journal, English

ISOLATION AND STRUCTURES OF TRANS-LAURENCENYNE, A POSSIBLE PRECURSOR OF THE C-15 HALOGENATED CYCLIC ETHERS, AND TRANS-NEOLAURENCENYNE FROM LAURENCIA-OKAMURAI
H KIGOSHI; Y SHIZURI; H NIWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 23, 14, 1475-1476, 1982, Peer-reviwed
Scientific journal, English

TOTAL SYNTHESIS OF AN ANTI-TUMOR ANTIBIOTIC, (+/-)-REDUCTIOMYCIN
M OJIKA; H NIWA; Y SHIZURI; K YAMADA
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, ROYAL SOC CHEMISTRY, 11, 628-629, 1982, Peer-reviwed
Scientific journal, English

STRUCTURE AND SYNTHESIS OF REDUCTILINE, A NOVEL METABOLITE FROM A VARIANT OF STREPTOMYCES-ORIENTALIS
M OJIKA; Y SHIZURI; H NIWA; K YAMADA; S IWADARE
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 23, 47, 4977-4980, 1982, Peer-reviwed
Scientific journal, English

(10R, 11R)-(+)-SQUALENE-10, 11-EPOXIDE - ISOLATION FROM LAURENCIA-OKAMURAI AND THE ASYMMETRIC-SYNTHESIS
H KIGOSHI; M OJIKA; Y SHIZURI; H NIWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 23, 51, 5413-5414, 1982, Peer-reviwed
Scientific journal, English

A CONVENIENT PREPARATION OF N-ACYLPYROGLUTAMIC ACID
K IMAKI; H NIWA; S SAKUYAMA; T OKADA; M TODA; M HAYASHI
CHEMICAL & PHARMACEUTICAL BULLETIN, PHARMACEUTICAL SOC JAPAN, 29, 9, 2699-2701, 1981, Peer-reviwed
Scientific journal, English

A NEW METHOD FOR CLEAVAGE OF ALIPHATIC METHYL ETHERS
H NIWA; T HIDA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 22, 42, 4239-4240, 1981, Peer-reviwed
Scientific journal, English

LAURENCENYNE, A PLAUSIBLE PRECURSOR OF VARIOUS NON-TERPENOID C-15-COMPOUNDS, AND NEOLAURENCENYNE FROM THE RED ALGA LAURENCIA-OKAMURAI
H KIGOSHI; Y SHIZURI; H NIWA; K YAMADA
TETRAHEDRON LETTERS, PERGAMON-ELSEVIER SCIENCE LTD, 22, 47, 4729-4732, 1981, Peer-reviwed
Scientific journal, English

Recent Studies on the Chemical Synthesis of Eicosanoids.
E. J. Corey; H. Niwa; J. R. Falck; C. Mioskowski; Y. Arai; A. Marfat
"Advances in Prostaglandin and Thromboxane Research" ed. by B. Samuelsson, P. W. Ramwell, and R. Paoletti, Raven Press, New York, 6, 19-25, 1980, Peer-reviwed
Scientific journal, English

Synthesis of 15,17-Methylene-prostaglandins.
Haruki Niwa; Masayasu Kurono
Chemistry Letters, 8, 1, 23-26, 1979, Peer-reviwed
Scientific journal, English

Synthesis of a New Prostaglandin Endoperoxide (PG H2) Analog and Its Function as an Inhibitor of the Biosynthesis of Thromboxane A2 (TX A2).
E. J. Corey; Haruki Niwa; Miriam Bloom; Peter W. Ramwell
Tetrachedron Letters, 8, 671-674, 1979, Peer-reviwed
Scientific journal, English

Selective Epoxidation of Eicosa-cis-5,8,11,14-tetraenoic(Arachidonic)Acid and Eicosa-cis-8,11,14-trienoic Acid.
E. J. Corey; Haruki Niwa; J. R. Falck
J. Am. Chem. Soc., 101, 6, 1586-1587, 1979, Peer-reviwed
Scientific journal, English

Total Synthesis of (S)-12 Hydroxy-5,8,14-cis-10-trans-eicosatetraenoic Acid(Samuelsson's HETE).
E. J. Corey; Haruki Niwa; Jochen Knolle
J. Am. Chem. Soc., 100, 6, 1942-1943, 1978, Peer-reviwed
Scientific journal, English

Synthesis of 15,19-Methano-ω-nor-prostaglandins.
Haruki Niwa; Masayasu Kurono
Chemistry Letters, 6, 10, 1211-1214, 1977, Peer-reviwed
Scientific journal, English

The Alkaloids from the Fruits of the Plant Daphniphyllaceae.
Masaaki Toda; Haruki Niwa; Hajime Irikawa; Yoshimasa Hirata; Shosuke Yamamura
Tetrahedron, 30, 16, 2683-2688, 1974, Peer-reviwed
Scientific journal, English

Chemical Studies on Nitrogen Heterocylic Skeleton of the Daphniphyllum Alkaloids.
Haruki Niwa; Masaaki Toda; Sueaki Ishimaru; Yoshimasa Hirata; Shosuke Yamamura
Tetrahedron, 30, 17, 3031-3036, 1974, Peer-reviwed
Scientific journal, English

The Structure of Daphniphyllidine.
Masaaki Toda; Haruki Niwa; Yoshimasa Hirata; Shosuke Yamamura
Tetrachedron Letters, 14, 11, 797-798, 1973, Peer-reviwed
Scientific journal, English

Biosynthesis of Daphniphyllum Alkaloids.
Kazuo T. Suzuki; Shigenobu Okuda; Haruki Niwa; Masaaki Toda; Yoshimasa Hirata; Shosuke Yamamura
Tetrachedron Letters, 14, 11, 799-802, 1973, Peer-reviwed
Scientific journal, English

Biosynthesis of Daphnilactone-B.
Haruki Niwa; Yoshimasa Hirata; Kazuo T. Suzuki; Shosuke Yamamura
Tetrachedron Letters, 14, 23, 2129-2132, 1973, Peer-reviwed
Scientific journal, English

2-Azabicyclo[3.3.1]non-1-ene Systems as Reaction Intermediates.
Masaaki Toda; Haruki Niwa; Kazuharu Ienaga; Yoshimasa Hirata; Shosuke Yamamura
Tetrachedron Letters, 13, 5, 335-338, 1972, Peer-reviwed
Scientific journal, English

Daphnilactone-B, a Major Alkaloid, from the Fruits of Daphniphyllaceae.
Haruki Niwa; Masaaki Toda; Yoshimasa Hirata; Shosuke Yamamura
Tetrachedron Letters, 13, 26, 2697-2700, 1972, Peer-reviwed
Scientific journal, English

生物発光の原理と応用
丹羽治樹
Jul. 2012, 自動車技術会 関東支部報「高翔」, 58, xx, Japanese, Introduction other

生物発光の原理と応用
丹羽治樹
Apr. 2012, 日本大気電気学会誌, 6, 1, 31-34, Japanese, Introduction other

オワンクラゲの生物発光機構
丹羽治樹
Apr. 2009, 岩波書店「科学」, 79, 4, 96-97, Japanese, Introduction other

生物はなぜ光るのか－生物発光とその応用－
丹羽治樹
Oct. 2005, ２００５第１９回「大学と科学」公開シンポジウム講演収録集 『不思議な生物現象の化学』, pp. 171-182, Japanese, Introduction other

Study on the bioluminescent mechanism of luminous snail Latia neritoides: the Km value of luciferase and the product analyses of bioluminescent reactions of the Latia luciferin analogs
MASAKI MIZUKI; MAMINO MASASHI; NAGAIE SATOSHI; NAKAMURA MITSUHIRO; KOJIMA SATOSHI; OMIYA YOSHIHIRO; MAKI SHOJIRO; HIRANO TAKASHI; NIWA HARUKI
11 Mar. 2005, 日本化学会講演予稿集, 85th, 2, 862, Japanese, 0285-7626, 200902221179445784

生物発光のメカニズムとその応用
丹羽治樹
2002, 現代化学, 379, 29-36, Japanese, Introduction other

The application of electroorganic chemical reaction
S Maki; H Niwa
The chemical, site-specific oxidations of saturated hydrocarbons as mimic for biological process are important subjects in synthetic organic chemistry. Such oxidations are seldom achieved in conventional chemistry. The development of such methodology is challenging, extensive studies which are currently ongoing in many laboratories. Recently we found that the electrochemical oxidation can achieve the site-specific hydroxylation of a certain inactivated methine and methylene groups in moderate or good yields. Further we achieved stereoselective chlorination of steroidal double bonds and selective cleavage of styrylic olefins as well as the triene of Vitamin D-2 by electrolysis. Descried herein are the scope and limitation, and the synthetic application of such electrochemical oxidation reactions., SOC SYNTHETIC ORGANIC CHEM JPN, Sep. 1998, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 56, 9, 725-735, Japanese, Peer-reviwed, Introduction other, 0037-9980, WOS:000076044300003

Baiotec Illustrated : Mechanism of Sensitized Bioluminescence of Aequorea victoria
Haruki Niwa
1998, Bioscience and Industry, 56, 7, 443, Japanese, Introduction other

Topics : Mechanism of Sensitized Bioluminescence of Aequorea victoria
Haruki niwa
1998, Bioscience and Industry, 56, 7, 471-472, Japanese, Introduction other

Luminous Reactions(Topics : Luminous Organisms)
haruki Niwa
裳華房, 1996, Idenn, 50, 11, 35-42, Japanese, Introduction other, 0387-0022, 40000132708, AN00015468

植物神経毒アニサチンの合成
丹羽治樹; 山田靜之
1991, ファルマシア(日本薬学会), 27, 7, 924-927, Japanese, Introduction other

植物起源の発がん物質の合成
山田靜之; 丹羽治樹; 木越英夫
1990, 化学増刊118「生体機能解明のための化学合成」 化学同人(京都), 191-201, Japanese, Introduction other

TOTAL SYNTHESIS OF POLYFUNCTIONALIZED, BIOLOGICALLY-ACTIVE NATURAL-PRODUCTS - SYNTHESIS OF MACROCYCLIC PYRROLIZIDINE ALKALOIDS
H NIWA
SOC SYNTHETIC ORGANIC CHEM JPN, Jul. 1988, JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN, 46, 7, 693-703, Japanese, Introduction other, 0037-9980, WOS:A1988P301900006

Total Synthesis of Sesquiterpenoids of Picrotoxane Type.
Haruki Niwa; Kiyoyuki Yamada
1986, J. Synth. Org. Chem., Jpn., 44, 3, 180-190, Japanese, Introduction other

医学のための細胞生物学：コラム「ＧＦＰと下村脩先生」
丹羽治樹; コラム執筆分担; 監修 永田和宏; 田浩平
Japanese, Joint work, 南山堂, Aug. 2009

岩波：科学 Vol. 71, No. 4 (2009).特集「クラゲ」-オワンクラゲの生物発光機構-
丹羽治樹
Japanese, Joint work, クラゲの生物発光, 岩波書店, Apr. 2009

天然物化学ー 海洋生物編： 1.2.7「海洋生物の発光現象」
丹羽治樹; 執筆分担; 監修 山村庄助; 長谷川宏司
Japanese, Joint work, 1.2.7「海洋生物の発光現象, アイピーシー, Jun. 2008

生物物理学ハンドブック： 7.6 生物発光
丹羽治樹
Japanese, Joint work, 7.6 生物発光, 朝倉書店, Apr. 2007

別冊『化学：分子イメージング最前線』 1.4 入門「自然界に光る生き物とその原理」
丹羽治樹
Japanese, Joint work, 1.4：入門「自然会の”光る生物”とその原理」, 化学同人, Apr. 2007

天然物化学ー植物編
丹羽治樹; 執筆分担; 監修 山村庄助; 長谷川宏司
Japanese, Joint work, 第３章 植物由来の生理活性天然有機化合物の合成 3.1.2 プタキロシン、アニサチン, アイピーシー, Feb. 2007

バイオサイエンス化学－生命から学ぶ化学－ 第４章 生命の物質－炭素化合物
新井孝夫; 大森大二郎; 立屋敷哲; 丹羽治樹
Japanese, Joint work, 第４章 生命の物質－炭素化合物, 東京化学同人, Mar. 2003

有機化学実験のてびき-3
丹羽治樹; 執筆分担; 監修 後藤俊夫; 芝 哲夫; 浦輝夫
Japanese, Joint work, 化学同人, 1990

有機化学実験のてびき-4
丹羽治樹; 執筆分担; 監修 後藤俊夫; 芝 哲夫; 浦輝夫
Japanese, Joint work, 化学同人, 1990

有機化学実験のてびき-1
丹羽治樹; 執筆分担; 監修 後藤俊夫; 芝 哲夫; 浦輝夫
Japanese, Joint work, 化学同人, 1988

生物発光、温故知新
丹羽治樹
Invited oral presentation, Japanese, 生物発光化学発光研究会第30学術講演会（東工大大岡山キャンパス, 目黒区）、抄録集PLxx（2013.11.02), 生物発光化学発光研究会第30学術講演会（東工大大岡山キャンパス, 目黒区）、抄録集PLxx（2013.11.02)
Nov. 2013

ホタル生物発光系をモデルとした人工発光系の創製と実用化
岩野 智; 伊藤 和人; 北田 昇雄; 牧 昌次郎; 丹羽 治樹
Others, Japanese, 第8回産学官連携DAY in 電通大 電気通信大学 産学官連携センター産学連携支援部門第１７回共同研究成果発表会(電気通信大学、調布）（2012.6.6), 第8回産学官連携DAY in 電通大 電気通信大学 産学官連携センター産学連携支援部門第１７回共同研究成果発表会(電気通信大学、調布）（2012.6.6)
Jun. 2012

生物発光の化学とその イメージングへの応用
丹羽治樹
Keynote oral presentation, Japanese, 平成19年度日本バイオイメージング学会公開講座 「理学と工学が拓くバイオイメージング」 (2007.10.31、東京理科大学野田キャンパス）, 平成19年度日本バイオイメージング学会公開講座 「理学と工学が拓くバイオイメージング」 (2007.10.31、東京理科大学野田キャンパス）, Domestic conference
Oct. 2007

生物発光研究の新展開：ラチア、ホタル、発光ゴカイ
丹羽治樹
Invited oral presentation, Japanese, 第八回神奈川ハイテク・リサーチ・センター研究発表会 (神奈川大学、2006.6.10), 第八回神奈川ハイテク・リサーチ・センター研究発表会 (神奈川大学、2006.6.10)
Jun. 2006

ホタルの光～生物の光通信～
丹羽治樹
Keynote oral presentation, Japanese, 『夏休み子供のための公開シンポジウム：生物の情報通信を探る』（平成１７年度文部科学省「科学研究補助金研究成果公開促進費」補助事業）補助資料(2005.8.9), Domestic conference
Aug. 2005

生物はなぜ光るのか－生物発光とその応用－
丹羽治樹
Keynote oral presentation, Japanese, 第１９回「大学と科学」公開シンポジウム 『不思議な生物現象の化学』, 第１９回「大学と科学」公開シンポジウム 『不思議な生物現象の化学』(2005.1.29), Domestic conference
Jan. 2005

Targetted Pursuit of Challenging Bioactive Molecules [Summary Report of Research Projekt (1999~2002)]
Haruki Niwa
Others, English, The Grant-in-Aid for Scientific Research on Priority Areas; The Ministry of Education, Culture, Sports, Scinece and Technology
Apr. 2004

巻き貝ラチア生物発光の分子機構
丹羽治樹
Invited oral presentation, Japanese, 日本化学会第80秋季年会（千葉,千葉）,講演予稿集，(2001.9.21)，（招待）
Sep. 2001

生物と光―生物発光の分子基盤研究とその応用
丹羽治樹
Invited oral presentation, Japanese, 第38回茅コンファランス「光科学の新しい展開とその応用」（福島，裏磐梯）
Nov. 2000

発光クラゲの緑色蛍光蛋白質（ＧＦＰ）の化学
丹羽治樹
Invited oral presentation, Japanese, 第１１回海洋生物活性 談話会（厚岸）（１９９７．５．２５）
May 1997

有機化学2
東邦大学大学院理学研究科

有機化学2
東邦大学大学院理学研究科

有機化学2
東邦大学大学院理学研究科

The Chemical Society of Japan

生物発光・化学発光研究会

検出装置、検出方法、及び検出器
Patent right, 山田幸夫, 西村吾朗, 丹羽治樹, 牧昌次郎, 道脇幸博, 小池卓二, 鈴木崇弘, 田代剛大, 特願2020-123183(優先権主張番号:特願2019-132298 出願日2019.7.17), Date applied: 17 Jul. 2020, 電気通信大学、北海道大学、昭和大学, 特開2021-16798, Date announced: 15 Feb. 2021, Domestic

特願2014-189314 新規複素環式化合物及びその塩、並びに、発光基質組成物(原特願2013-198998; 2013/9/25)
Patent right, 牧 昌次郎, 丹羽治樹, 特願2014-189314(原特願2013-198998; 2013/9/25), Date applied: 17 Sep. 2014, The University of Electro-Communications, 特開2015-193584, Date announced: 05 Nov. 2015, 特許第6353751, Date issued: 15 Jun. 2018

特願2013-530040：ルシフェラーゼの発光基質
Patent right, 西山 繁, 齋藤 毅, 牧 昌次郎, 丹羽治樹, 特願2013-530040, Date applied: 22 Aug. 2012, 国立大学法人 電気通信大学, WO/2013/027770 A1, Date announced: 28 Feb. 2013, 特許第6049019, Date issued: 02 Dec. 2016

特願2013-097755 新規ハロゲン化水素塩
Patent right, 牧 昌次郎, 丹羽治樹, 特願2013-097755, Date applied: 07 May 2013, 国立大学法人電気通信大学, 特開2014-218456, Date announced: 20 Nov. 2014, 特許第6011974号, Date issued: 30 Sep. 2016

PCT/JP2012/071207 (特願2011-182224) Int. Appl.Luciferin analog and its use for luminescent substrate for luciferase and luminescence detection kit
Patent right, Nishiyama, Shigeru, Saito, Tsuyoshi, Maki, Shojiro, Niwa, Haruk, PCT/JP2012/071207, Date applied: 22 Aug. 2012,  The University of Electro-Communications, Japan, CN103796999A, Date announced: 14 May 2014, ZL201280041269.3, Date issued: 22 Jul. 2015

特願2010-137031 遷移元素触媒およびその製造方法、並びに選択的水素添加方法
Patent right, 牧昌次郎, 丹羽治樹, 特願2010-137031, Date applied: 16 Jun. 2010, 国立大学法人電気通信大学, 特開2011-020116, Date announced: 03 Feb. 2011, 特許第5605619, Date issued: 05 Sep. 2014

PCT/JP2012/071207 (特願2011-182224) Int. Appl.Luciferin analog and its use for luminescent substrate for luciferase and luminescence detection kit
Patent right, Nishiyama, Shigeru, Saito, Tsuyoshi, Maki, Shojiro, Niwa, Haruk, PCT/JP2012/071207, Date applied: 22 Aug. 2012,  The University of Electro-Communications, Japan, US2014-0221665A1, Date announced: 07 Aug. 2014

PCT/JP2012/071207 (特願2011-182224) Int. Appl.Luciferin analog and its use for luminescent substrate for luciferase and luminescence detection kit
Patent right, Nishiyama, Shigeru, Saito, Tsuyoshi, Maki, Shojiro, Niwa, Haruk, PCT/JP2012/071207, Date applied: 22 Aug. 2012,  The University of Electro-Communications, Japan, EP2754657A1, Date announced: 16 Jul. 2014

特願2012-265382 環化化合物の製造方法、及び、環化化合物を含有する溶液の発光方法
Patent right, 斎藤 毅, 西山 繁, 井岡秀二, 牧 昌次郎, 丹羽治樹, 特願2012-265382, Date applied: 04 Dec. 2012, 学校法人慶応義塾、国立大学法人電気通信大学, 特開2014-108957, Date announced: 12 Jun. 2014

特願2009-064595：波長が制御されたルシフェラーゼの発光基質および製造方法
Patent right, 牧 昌次郎, 小島 哲, 丹羽治樹, 特願2009-064595, Date applied: 17 Mar. 2009, The University of Electro-Communications, 特開2010-215795, Date announced: 30 Sep. 2010, 特許第5550035号, Date issued: 30 May 2014

特願2008-023396:「ルシフェラーゼの発光基質」
Patent right, 牧 昌次郎, 小島 哲, 丹羽 治樹, 特願2008-023396, Date applied: 02 Feb. 2008, 国立大学法人電気通信大学, 特開2009-184932, Date announced: 20 Aug. 2009, 特許第5464311, Date issued: 31 Jan. 2014

特願2012-049619：ルシフェラーゼの発光基質
Patent right, 牧 昌次郎, 丹羽 治樹, 特願2012-49619, Date applied: 06 Mar. 2012, 国立大学法人 電気通信大学, 特開2013-184909, Date announced: 19 Sep. 2013

PCT/JP2012/071207 (特願2011-182224) Int. Appl.Luciferin analog and its use for luminescent substrate for luciferase and luminescence detection kit
Patent right, Nishiyama, Shigeru, Saito, Tsuyoshi, Maki, Shojiro, Niwa, Haruk, PCT/JP2012/071207, Date applied: 22 Aug. 2012,  The University of Electro-Communications, Japan, WO/2013/027770 A1, Date announced: 28 Feb. 2013

HETEROCYCLIC COMPOUND AND LUMINESCENCE METHOD
Patent right, 牧 昌次郎, 小島 哲, 丹羽治樹, 平野 誉, PCT/JP2007/056227, Date applied: 26 Mar. 2007, The University of Electro-Communications, WO2007/116687, Date announced: 18 Oct. 2007, 特許第5194258号, Date issued: 15 Feb. 2013

特願2011-108654 蛍光色素
Patent right, 平野 誉, 中川 達規, 牧 昌次郎, 丹羽治樹, 特願2011-108654, Date applied: 13 May 2011, 国立大学法人 電気通信大学, 特開2012-241014, Date announced: 10 Dec. 2012

（取下げ擬制）特願2011-182224：ルシフェラーゼの発光基質
Patent right, 西山 繁, 齋藤 毅, 牧 昌次郎, 丹羽治樹, (取下げ擬制)特願2011-182224, Date applied: 24 Aug. 2011, 国立大学法人 電気通信大学

特願2009-187979：抗体－ルシフェリルペプチド複合体、これを用いた被検物質の測定方法及び被検物質の測定試薬並びに測定試薬の調製方法
Patent right, 志賀 一樹, 河口 成, 牧 昌次郎, 丹羽 治樹, 特願2009-187979, Date applied: 14 Aug. 2009, キッコーマン株式会社、国立大学法人電気通信大学、株式会社キャンパスクリエイト, 特開2011-037791, Date announced: 24 Feb. 2011

特願2004-379971：天然型L-システインまたはその誘導体を用いたホタル発光基質の生合成システム及び本システムを含んだ発光基質溶液
Patent right, 近江谷克裕, 丹羽一樹, 丹羽治樹, 中村光裕, 龍福正行, 特願2004-379971, Date applied: 28 Dec. 2004, 産業技術総合研究所、電気通信大学、東洋ビーネット, 特開2006-180825, Date announced: 13 Jul. 2006, 特許4682310, Date issued: 18 Feb. 2011

PCT/JP2009/000376：ルシフェラーゼの発光基質
Patent right, 牧 昌次郎, 小島 哲, 丹羽治樹, PCT/JP2009/000376, Date applied: 02 Feb. 2009, The University of Electro-Communications, US2011/033878A1, Date announced: 10 Feb. 2011

PCT/JP2010/053177波長が制御されたルシフェラーゼの発光基質および製造方法
Patent right, 牧,小島,丹羽, PCT/JP2010/053177, Date applied: 28 Feb. 2010, The University of Electro-Communications, WO/2010/106896 A1, Date announced: 23 Sep. 2010

特願2009-027654 ルシフェラーゼの発光基質
Patent right, 牧 昌次郎, 小島 哲, 丹羽治樹, 特願2009-027654, Date applied: 09 Feb. 2009, The University of Electro-Communications, 特開2010-180191, Date announced: 19 Aug. 2010

特願2004-067098: イミダゾピラジノン誘導体及びビスアミノピラジノン誘導体並びに化学発光物質
Patent right, 特願2004-067098, Date applied: 10 Mar. 2004, 三菱科学(株), 特開2005-255579, Date announced: 22 Sep. 2005, 特許4561132, Date issued: 06 Aug. 2010

特願2008-244890［アシルアミノピラジナート-O,N］ーボロン誘導体および蛍光色素
Patent right, 平野 誉, 牧 昌次郎, 丹羽治樹, 特願2008-244890, Date applied: 24 Sep. 2008, The University of Electro-Communications, 特開2010-077040, Date announced: 08 Apr. 2010

特願2008-192596: ε-N-ルシフェリルリシン化合物、これを用いたペプチド標識剤及びペプチド標識方法
Patent right, 牧 昌次郎, 小島 哲, 丹羽 治樹, 河口 成, 特願2008-192596, Date applied: 25 Jul. 2008, 電気通信大学、キッコーマン株式会社、株式会社キャンパスクリエイト, 特開2010-30918, Date announced: 12 Feb. 2010

特願2003-195905: ビスイミダゾピラジノン系新規蛍光性・化学発光生物質
Patent right, 平野 誉, 丹羽治樹, 牧 昌次郎, 特願2003-195905:, Date applied: 11 Jul. 2003, 三菱化学, 特開2005-29500, Date announced: 03 Feb. 2005, 特許4363098, Date issued: 28 Aug. 2009

特願2003-026134: 還元触媒及びその製造方法、並びに選択的水素添加方法
Patent right, 牧 昌次郎, 丹羽治樹, 特願2003-026134, Date applied: 02 Feb. 2003, Japan Science and Technology Agency, 特開2004-23714, Date announced: 26 Aug. 2004, 特許4116891, Date issued: 25 Apr. 2008

特願2006-086175:複素環化合物及び発光方法
Patent right, 牧 昌次郎, 小島 哲, 丹羽治樹, 平野 誉, 特願2006-086175, Date applied: 27 Mar. 2006, The University of Electro-Communications, 特開2007-194258, Date announced: 02 Aug. 2007

特願2002-33258: パラジウム触媒を用いた選択的水素添加反応方法
Patent right, 牧 昌次郎, 丹羽治樹, 佐野淳典, 特願2002-33258, Date applied: 08 Feb. 2002, 和光純薬工業 (株), 特開2003-238482, Date announced: 27 Aug. 2003, 特許第3976579, Date issued: 29 Jun. 2007

特願2005-031574:複素環化合物及び発光甲虫ルシフェラーゼ発光系用発光物質
Patent right, 丹羽治樹, 牧昌次郎, 平野 誉, 特願2005-031574, Date applied: 08 Feb. 2005, The University of Electro-Communications, 特開2006-219381, Date announced: 24 Aug. 2006

SYSTEM FOR BIOSYNTHESIS OF FIREFLY LUMINESCENCE SUBSTRATES WITH NATURAL L-CYSTEINE OR DERIVATIVES THEREOF AND LUMINESCENCE SUBSTRATE SOLUTIONS CONTAINING THE SYSTEM
Patent right, 近江谷克裕, 丹羽一樹, 丹羽治樹, 中村光裕, 龍福正行, PCT/JP2005/023847, Date applied: 27 Dec. 2005, 産業技術総合研究所、電気通信大学、東洋ビーネット, WO/2006/070775, Date announced: 06 Jul. 2006

特願2003-292606: 発光キノコヤコウタケの簡便栽培法
Patent right, 杉本正志, 丹羽治樹, 特願2003-292606, Date applied: 09 Jul. 2003, 杉本正志, 特開2005-27634, Date announced: 03 Feb. 2005

特願2003-116616: 芳香族有機化合物の分解方法
Patent right, 牧昌次郎, 丹羽治樹, 平野 誉, 特願2003-116616, Date applied: 22 Apr. 2003, Japan Science and Technology Agency, 特開2004-321275, Date announced: 18 Nov. 2004

特願2002-80931: 新規なパラジウム触媒
Patent right, 牧昌次郎, 丹羽治樹, 佐野淳典, 大野桂二, 特願2002-80931, Date applied: 22 Mar. 2002, 和光純薬工業 (株)., 特開2003-275593, Date announced: 30 Sep. 2003

特願2002-80930: パラジウムブラックの新規な製造方法
Patent right, 牧 昌次郎, 丹羽 治樹, 佐野 淳典, 大野 桂二, 特願2002-80930, Date applied: 22 Mar. 2002, 和光純薬工業 (株), 特開2003-275586, Date announced: 30 Sep. 2003

特願2002-80929: 担持型パラジウム触媒
Patent right, 牧昌次郎, 丹羽治樹, 佐野淳典, 大野桂二, 特願2002-80929, Date applied: 22 Mar. 2002, 和光純薬工業 (株)., 特開2003-275585, Date announced: 30 Sep. 2003

特願2000-340644: アルケン類の選択的水素添加反応並びにこれに用いる触媒及び触媒構造体
Patent right, 小泉 恵, 錦 善則, 古田 常人, 丹羽 治樹, 牧 昌次郎, 特願2000-340644, Date applied: 08 Nov. 2000, ペルメレック電極 (株)., 特開2002-145818, Date announced: 22 May 2002

特願2000-133584: アルケン類の選択的水素添加方法
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特願平11-137401: アルケンの選択的水素添加方法
Patent right, 吉田泰樹, 尾形節郎, 井上博史, 岩倉千秋, 丹羽治樹, 牧昌次郎, 特願平11-137401, Date applied: 18 May 1999, ペルメレック電極 (株), 特開2000-328278, Date announced: 28 Nov. 2000

特開昭52-91847: プロスタグランジン関連化合物
Patent right, 小野薬品工, 特願昭52-4888, Date applied: 21 Jan. 1977, 特開昭52-91847, Date announced: 02 Aug. 1977

特開昭52-77027: 2－(4－イソブチルフェニル)プロピオン酸
Patent right, 黒野昌庸, 戸田正明, 丹羽治樹, 特願昭50-151984, Date applied: 22 Dec. 1975, 小野薬品工業株式会社, 特開昭52-77027, Date announced: 29 Jun. 1977

特開昭52-62237: α置換フェニル・アルカン・カルボン酸の製造法
Patent right, 黒野昌庸, 戸田正明, 丹羽治樹, 小菅俊士, 飯田貴史, 成田研一, 特願昭50-138041, Date applied: 19 Nov. 1975, 小野薬品工業(株), 特開昭52-62237, Date announced: 23 May 1977

特開昭52-53833: α置換フェニル・アルカン・カルボン酸の製造法
Patent right, 黒野昌庸, 戸田正明, 丹羽治樹, 特願昭50-128906, Date applied: 28 Oct. 1975, 小野薬品工業(株), 特開昭52-53833, Date announced: 30 Apr. 1977

特開昭51-86447: 1β，5β－2－オキサ－3－ヒドロキシ－6β－置換メチル－7α－置換オキシ－ビシクロ［3.3.0］オクタン類の製造法
Patent right, 黒野昌庸, 丹羽治樹, 特願昭50-9884, Date applied: 24 Jan. 1975, 小野薬品工業(株)., 特開昭51-86447, Date announced: 29 Jul. 1976