研究者詳細 - 布施　新一郎

Microflow Synthesis of Unsymmetrical H-Phosphonates via Sequential and Direct Substitution of Chlorine Atoms in Phosphorus Trichloride with Alkoxy Groups. 査読有り

Tanaka Y, Kitamura H, Fuse S

The Journal of organic chemistry 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Organic Chemistry

DOI： 10.1021/acs.joc.3c02467

Multi-objective Bayesian optimisation using q-noisy expected hypervolume improvement (qNEHVI) for the Schotten-Baumann reaction 査読有り国際共著

Zhang, JYZ; Sugisawa, N; Felton, KC; Fuse, S; Lapkin, AA

REACTION CHEMISTRY & ENGINEERING 9 巻 ( 3 ) 頁： 706 - 712 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Reaction Chemistry and Engineering

Amide bond formation is one of the most prevalent reactions in the pharmaceutical industry, among which the Schotten-Baumann reaction with a long history is useful as a potential green amide formation approach. However, the use of water in the reaction system often causes undesired hydrolysis and can generate a multiphase system. This makes the reaction space complex, making it challenging to find the optimal conditions. In this study, the Schotten-Baumann reaction was studied in a continuous flow and was optimised with two objectives using a Bayesian optimisation algorithm based on the q-noisy expected hypervolume improvement (qNEHVI) acquisition function. The algorithm guided the experiment design over a range of electrophiles, equivalents, solvents, and flow rates, and was able to identify the Pareto front of optimal solutions efficiently. Based on the optimisation results, reactions under a flow and batch conditions were compared; undesired hydrolysis was suppressed successfully using the flow conditions. Finally, the relationship between the solvent and flow rate was discussed to gain more insights into this reaction.

DOI： 10.1039/d3re00502j

One-Flow Synthesis of Substituted Indoles via Sequential 1,2-Addition/Nucleophilic Substitution of Indolyl-3-Carbaldehydes 査読有り

Fuse, S; Kanda, S; Masui, H

CHEMISTRY-AN ASIAN JOURNAL 19 巻 ( 1 ) 頁： e202300909 2023年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Chemistry - An Asian Journal

DOI： 10.1002/asia.202300909

Switchable Synthesis of 7-and 14-Membered Cyclic Peptides Containing N-Methyl- and & beta;-Amino Acids Utilizing Microflow Technology 査読有り

Fuse Shinichiro, Okabe Ren

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 26 巻 ( 35 ) 頁： e202300700 2023年8月

出版者・発行元：European Journal of Organic Chemistry

Smaller cyclic peptides containing non-proteinogenic amino acids have garnered much attention for use as drugs, but their chemical synthesis is extremely challenging. In this study, a rapid (60.5 min) synthesis of 7- and 14-membered cyclic peptides containing N-methyl- and β-amino acids was achieved by only switching the concentrations (0.20 M or 0.01 M) of the substrates. The developed approach required neither expensive transition-metals nor expensive coupling agents. As far as we could ascertain, this is the first report of the synthesis of smaller (≤16-membered) cyclic N-methylated peptides via dimerization-cyclization strategy.

DOI： 10.1002/ejoc.202300700

Rapid and column-chromatography-free peptide chain elongation via a one-flow, three-component coupling approach 査読有り

Sugisawa Naoto, Ando Akira, Fuse Shinichiro

Chemical Science 14 巻 ( 25 ) 頁： 6986 - 6991 2023年6月

One-Flow Syntheses of Unsymmetrical Sulfamides and N-Substituted Sulfamate Esters 招待有り査読有り

Sugisawa Naoto, Nakabayashi Kohei, Sugisawa Hiroki, Fuse Shinichiro

ORGANIC LETTERS 26 巻 ( 14 ) 頁： 2739 - 2744 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Organic Letters

We developed one-flow syntheses of unsymmetrical sulfamides and N-substituted sulfamate esters by changing a nucleophile and a tertiary amine from inexpensive and commercially available chlorosulfonic acid. In the synthesis of N-substituted sulfamate esters, unexpected symmetrical sulfite formation was suppressed by changing the tertiary amine. The effect of tertiary amines was proposed using linear regression. Our approach rapidly (≤90 s) provides desired products containing acidic and/or basic labile groups without tedious purification under mild (20 °C) conditions.

DOI： 10.1021/acs.orglett.3c01546

Continuous-/Micro-Flow Reactions Using Highly Electrophilic PCl3 and POCl3. 招待有り査読有り

Kitamura H, Fuse S

ChemPlusChem 88 巻 ( 6 ) 頁： e202300176 2023年6月

Peptide Cyclization by the Use of Acylammonium Species 査読有り

Shamoto Otoka, Komuro Keiji, Sugisawa Naoto, Chen Ting-Ho, Nakamura Hiroyuki, Fuse Shinichiro

Angewandte Chemie International Edition 62 巻 ( 27 ) 頁： e202300647 2023年5月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Angewandte Chemie - International Edition

Although cyclic peptides have become increasingly important as drugs, the most conventional peptide cyclization method using moderately active coupling agents suffers from a lot of waste and high cost as well as long reaction times and burdensome purification. Herein, we report an unconventional approach to peptide cyclization that uses acylammonium species generated from inexpensive and less wasteful Me2NBn and ClCO2i-Pr. Using this approach, we observed the desired rapid activation of the C-terminus of cyclization precursors by an acylammonium ion for rapid and epimerization/dimerization-free cyclization of synthetically challenging peptides, including a difficult cyclization involving N-methyl amide bond formation. The ease of purification, productivities, and reaction mass efficiencies of our approach were significantly superior to those in previous reports. We synthesized a previously reported versicotide D analogue, and our data indicated that its assigned stereostructure should be revised.

DOI： 10.1002/anie.202300647

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution 査読有り

Hisashi Masui, Sena Kanda, Shinichiro Fuse

Communications Chemistry 6 巻頁： 47 2023年3月

A liquid-phase continuous-flow peptide synthesizer for preparing C-terminal free peptides 査読有り

Yuma Otake, Kyohei Adachi, Yoshiaki Yamashita, Natsumi Iwanaga, Hirokatsu Sunakawa, Taiki Shamoto, Jun-ichi Ogawa, Atsushi Ito, Yutaka Kobayashi, Keiichi Masuya, Shinichiro Fuse, Daisuke Kubo, Hidenosuke Itoh

Reaction Chemistry & Engineering 8 巻 ( 4 ) 頁： 863 - 870 2022年12月

Micro-flow N-acylation using highly electrophilic acyl ammonium cations for peptide and urethane-protected N-carboxyanhydride syntheses 招待有り査読有り

Hisashi Masui, Shinichiro Fuse

Journal of Synthetic Organic Chemistry, Japan 80 巻 ( 11 ) 頁： 986 - 993 2022年11月

Sequential Nucleophilic Substitution of Phosphorus Trichloride with Alcohols in a Continuous-Flow Reactor and Consideration of a Mechanism for Reduced Over-reaction through the Addition of Imidazole 査読有り

Hiroshi Kitamura, Yuma Otake, Naoto Sugisawa, Hiroki Sugisawa, Tomonori Ida, Hiroyuki Nakamura, Shinichiro Fuse

CHEMISTRY-A EUROPEAN JOURNAL 28 巻 ( 37 ) 頁： e202200932 2022年7月

Recent Advances in the Solid- and Solution-Phase Synthesis of Peptides and Proteins Using Microflow Technology 招待有り査読有り

Masui Hisashi, Fuse Shinichiro

ORGANIC PROCESS RESEARCH & DEVELOPMENT 26 巻 ( 6 ) 頁： 1751 - 1765 2022年6月

担当区分：最終著者,　責任著者記述言語：日本語出版者・発行元：Organic Process Research and Development

Peptides have become increasingly important as drugs and drug candidates. In particular, specialty peptides have garnered considerable attention in recent years because of their improved metabolic stability, higher affinity, and biological target selectivity; some of them have the ability to enable cell membrane permeation and oral administration. Despite its long history, peptide synthesis has various limitations, such as high cost, generation of large amounts of waste, and the requirement for hazardous reagents and solvents. Microflow synthesis, wherein the inner diameter of the reaction tube is ≤1 mm, presents several advantages compared with conventional batch synthesis, such as precise control of the reaction time on a short scale, precise reaction temperature control, and facile scale-up with high reproducibility. Microflow technology has been utilized for peptide synthesis since the beginning of the 21st century. The advantages of microflow synthesis enable the use of highly active and unstable chemical species or high-Temperature conditions that accelerate peptide synthesis. The combined use of microflow technology, automated synthesis, and online monitoring technologies has emerged in recent years. This approach not only improved the synthetic efficiency but also afforded large amounts of reliable data that can be used to train machine learning models. This review summarizes the solid-and solution-phase syntheses of α-peptides and specialty peptides, including N-methylated peptides, β-peptides, and cyclic peptides, reported mainly after 2017. The recently reported mesoflow peptide syntheses (inner diameter of the reaction channels > 1 mm), the microflow automated syntheses, and in-line analysis are covered in this review.

DOI： 10.1021/acs.oprd.2c00074

Continuous-Flow Synthesis of N-Methylated Peptides via Generation of an Acyl N-Methylimidazolium Cation.

A micro-flow rapid dual activation approach for urethane-protected alpha-amino acid N-carboxyanhydride synthesis 査読有り

Okabe Ren, Sugisawa Naoto, Fuse Shinichiro

ORGANIC & BIOMOLECULAR CHEMISTRY 20 巻 ( 16 ) 頁： 3303 - 3310 2022年3月

Masui H, Fuse S

Chemical Protein Synthesis 2530 巻頁： 45 - 53 2022年

記述言語：英語出版者・発行元：Methods in Molecular Biology

A detailed protocol is described for the continuous-flow synthesis of N-methylated peptides. N-Methylated peptides are very important class of bioactive compounds compared with normal peptides because they can enhance oral bioavailability, cell membrane permeability, and stability against enzymatic degradation. In our developed flow synthesis, a variety of N-methylated dipeptides is obtained in high yields without severe racemization from equivalent amounts of amino acids. The addition of a strong Brønsted acid is critical to generate the highly reactive N-methylimidazolium cation species to accelerate the amidation. The developed approach enabled the synthesis of a bulky peptide with a higher yield in a shorter amount of time compared with the results of conventional amidation.

DOI： 10.1007/978-1-0716-2489-0_4

マイクロフロー合成法を駆動力とするペプチド合成の革新

Rapid and mild one-flow synthetic approach to unsymmetrical sulfamides guided by Bayesian optimization 査読有り国際共著

Naoto Sugisawa, Hiroki Sugisawa, Yuma Otake, Roman V. Krems, Hiroyuki Nakamura, Shinichiro Fuse

Chemistry -Methods 1 巻 ( 11 ) 頁： 484 - 490 2021年8月

有機合成化学は面白い！

布施新一郎

有機合成化学協会誌 79 巻 ( 4 ) 頁： 346 - 348 2021年4月

Rapid and mild lactamization using highly electrophilic triphosgene in a micro-flow reactor, 査読有り

Shinichiro Fuse, Keiji Komuro, Yuma Otake, Hisashi Masui, Hiroyuki Nakamura

Chemistry a European Journal 27 巻 ( 27 ) 頁： 7525 - 7532 2021年1月

Cluster Preface: Integrated Synthesis Using Continuous-Flow Technologies 招待有り

Fuse Shinichiro

SYNLETT 31 巻 ( 19 ) 頁： 1878 - 1879 2020年12月

Recent Advances in Continuous-Flow Reactions Using Metal-Free Homogeneous Catalysts 招待有り査読有り

Naoto Sugisawa, Hiroyuki Nakamura, Shinichiro Fuse

Catalysts 10 巻 ( 11 ) 頁： 1321 2020年11月

布施新一郎

MEDCHEM NEWS 30 巻 ( 4 ) 頁： 193 - 200 2020年11月

記述言語：日本語出版者・発行元：公益社団法人日本薬学会

ペプチド医薬品はその重要性を増しており、特に近年では、環状ペプチドやN-メチル化ペプチドを含む特殊ペプチドが注目を集めている。一方で、これらペプチドの低コスト生産の実現は未だ道半ばである。Theodor Curtiusによる初のペプチド結合形成の報告から140年近くの歳月が経過し、すでに無数の合成法が開発されてきた中でペプチド合成に革新を起こすことは極めて挑戦的な課題といえる。1990年代半ばに登場した、微小な流路を反応場とするマイクロフロー合成法は、これまでのバッチリアクターの利用を基盤とする合成法では制御困難な反応に新たな価値を付与するものである。本稿ではペプチド合成に革新を起こすべく推進してきた、マイクロフロー合成法を駆使したアミド化反応の開発について紹介する。

DOI： 10.14894/medchem.30.4_193

CiNii Research

Size-Controllable and Scalable Production of Liposomes Using a V-Shaped Mixer Micro-Flow Reactor

Kawamura Jun, Kitamura Hiroshi, Otake Yuma, Fuse Shinichiro, Nakamura Hiroyuki

ORGANIC PROCESS RESEARCH & DEVELOPMENT 24 巻 ( 10 ) 頁： 2122 - 2127 2020年10月

記述言語：日本語出版者・発行元：Organic Process Research and Development

The use of microfluidics has been regarded as a promising solution for the costly and complex preparation of liposomes, and the development of controllable and scalable liposome production using simple-structured, readily available, and inexpensive "off-the-shelf"microfluidics remains important pursuit. We have achieved simple and inexpensive production of liposomes using an off-the-shelf V-shaped mixer. The size of liposomes was controlled (50-70 nm diameter, PDI < 0.1) in the desired range (<100 nm) by changing the relative flow rate of the ethanol solution of lipids and the aqueous solution. The developed approach is scalable (12 mL/min), and several representative lipids, including inexpensive Span 60, can be used for the preparation of nanoparticles.

DOI： 10.1021/acs.oprd.0c00174

Single-Step, Rapid, and Mild Synthesis of beta-Amino Acid N-Carboxy Anhydrides Using Micro-Flow Technology

Size-controllable and scalable production of liposomes using a V-shape mixer micro-flow reactor 招待有り査読有り

Jun Kawamura, Hiroshi Kitamura, Yuma Otake, Shinichiro Fuse, Hiroyuki Nakamura

Organic Process Research and Development 24 巻 ( 10 ) 頁： 2122 - 2127 2020年6月

Investigation into the influence of an acrylic acid acceptor in organic D-π-A sensitizers against phototoxicity 査読有り

Shinichiro Fuse, Wataru Moriya, Shinichi Sato, Hiroyuki Nakamura

Bioorganic and Medicinal Chemistry 28 巻 ( 13 ) 頁： 115558 2020年5月

Photochemical Conversion of Isoxazoles to 5-Hydroxyimidazolines. 査読有り

Morita T, Fuse S, Nakamura H

Organic letters 22 巻 ( 9 ) 頁： 3460 - 3463 2020年5月

N-Methylated Peptide Synthesis via Acyl N-Methylimidazolium Cation Generation Accelerated by a Brønsted Acid. 査読有り

Yuma Otake, Yusuke Shibata, Yoshihiro Hayashi, Susumu Kawauchi, Hiroyuki Nakamura, Shinichiro Fuse

Angewandte Chemie (International ed. in English) 59 巻 ( 31 ) 頁： 12925 - 12930 2020年4月

Micro-flow synthesis of β-amino acid derivatives via a rapid dual activation approach. 査読有り

Naoto Sugisawa, Hiroyuki Nakamura, Shinichiro Fuse

Chemical communications (Cambridge, England) 56 巻頁： 4527 - 4530 2020年4月

Sugisawa Naoto, Otake Yuma, Nakamura Hiroyuki, Fuse Shinichiro

CHEMISTRY-AN ASIAN JOURNAL 15 巻 ( 1 ) 頁： 79 - 84 2020年1月

記述言語：日本語出版者・発行元：Chemistry - An Asian Journal

β-Amino acid N-carboxy anhydrides (β-NCAs) are rarely used in the synthesis of β-peptides, which is due mainly to the poor availability of these potentially useful substrates. Herein, we describe the heretofore challenging synthesis of β-NCAs via a single-step, rapid, and mild formation using pH flash switching and flash dilution, which are aspects of micro-flow technology. We synthesized 15 β-NCAs in good to excellent yields that included acid-labile β-NCAs that cannot be readily synthesized using the conventional Leuchs approach. Scaled-up synthesis using this process can be readily achieved via continuous operation.

DOI： 10.1002/asia.201901429

Cover Feature: Peptide‐Chain Elongation Using Unprotected Amino Acids in a Micro‐Flow Reactor (Chem. Eur. J. 66/2019) 査読有り

Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity.

Fuse S, Suzuki K, Kuchimaru T, Kadonosono T, Ueda H, Sato S, Kizaka-Kondoh S, Nakamura H

Bioorganic & medicinal chemistry 28 巻 ( 1 ) 頁： 115207 2020年1月

マイクロフロー合成技術による次世代医薬品（ペプチド）合成法の開発

布施新一郎

月刊 PHARMSTAGE 11 巻頁： 13 - 22 2020年

Design, synthesis, and evaluation of azo D-π-A dyes as photothermal agents. 査読有り

Fuse S, Oishi T, Matsumura K, Hayashi Y, Kawauchi S, Nakamura H

Organic & biomolecular chemistry 18 巻 ( 1 ) 頁： 93 - 101 2019年12月

The design, synthesis, and evaluation of azo D-π-A dyes as photothermal agents 査読有り

Shinichiro Fuse, Tsukasa Oishi, Keisuke Matsumura, Yoshihiro Hayashi, Susumu Kawauchi, Hiroyuki Nakamura

Organic and Biomolecular Chemistry 18 巻 ( 1 ) 頁： 93-101 2019年12月

Single-step, rapid, and mild synthesis of β-amino acid N-carboxy anhydrides using micro-flow technology 査読有り

Naoto Sugisawa, Yuma Otake, Hiroyuki Nakamura, and Shinichiro Fuse

Chemistry an Asian Journal 15 巻 ( 1 ) 頁： 79-84 2019年11月

Peptide chain elongation using unprotected amino acids in a micro-flow reactor 査読有り

Shinichiro Fuse, Koshiro Masuda, Yuma Otake, Hiroyuki Nakamura

Chemistry a European Journal 25 巻 ( 66 ) 頁： 15091-15097 2019年11月

Peptide-Chain Elongation Using Unprotected Amino Acids in a Micro-Flow Reactor. 査読有り

Fuse S, Masuda K, Otake Y, Nakamura H

Chemistry (Weinheim an der Bergstrasse, Germany) 25 巻 ( 66 ) 頁： 15091 - 15097 2019年11月

Design, synthesis, and evaluation of indeno[2,1-c]pyrazolones for use as inhibitors against hypoxia-inducible factor (HIF)-1 transcriptional activity 査読有り

Shinichiro Fuse, Kensuke Suzuki, Takahiro Kuchimaru, Tetsuya Kadonosono, Hiroki Ueda, Shinichi Sato, Shinae Kizaka-Kondo, and Hiroyuki Nakamura

Bioorganic and Medicinal Chemistry 28 巻頁： 115207 2019年11月

Shinichiro Fuse, Koshiro Masuda, Yuma Otake, Hiroyuki Nakamura

Chemistry – A European Journal 2019年11月

Donor-acceptor polymers containing thiazole-fused benzothiadiazole acceptor units for organic solar cells 査読有り

Tomoya Nakamura, Yasuhisa Ishikura, Noriko Arakawa, Megumi Hori, Motoi Satou, Masaru Endo, Hisashi Masui, Shinichiro Fuse, Takashi Takahashi, Yasujiro Murata, Richard Murdey, Atsushi Wakamiya

RSC Advances 9 巻 ( 13 ) 頁： 7107-7114 2019年3月

Donor-acceptor polymers containing thiazole-fused benzothiadiazole acceptor units for organic solar cells.

Nakamura T, Ishikura Y, Arakawa N, Hori M, Satou M, Endo M, Masui H, Fuse S, Takahashi T, Murata Y, Murdey R, Wakamiya A

RSC advances 9 巻 ( 13 ) 頁： 7107 - 7114 2019年3月

Peptide Synthesis Utilizing Micro-flow Technology. 査読有り

Fuse S, Otake Y, Nakamura H

Chemistry, an Asian journal 13 巻 ( 24 ) 頁： 3818 - 3832 2018年12月

Elucidating the mode of action for thiophene-based organic D-π-A sensitizers for use in photodynamic therapy 査読有り

Shinichiro Fuse, Miori Takizawa, Shinichi Sato, Shigetoshi Okazaki, Hiroyuki Nakamura,

Bioorganic and Medicinal Chemistry 27 巻 ( 2 ) 頁： 315-321 2018年12月

Synthesis of 3-hydroxy-4-substituted-picolinonitriles from 4-propargylaminoisoxazoles via stepwise and one-pot isoxazolopyridine formation/N-O bond cleavage sequence 査読有り

Shintaro Fukuhara, Somaraju Yugandar, Shinichiro Fuse, Hiroyuki Nakamura

3 巻 ( 12 ) 頁： 16472-16476 2018年12月

The design, synthesis, and evaluation of organic dithienopyrrole-based D-pai-A dyes for use as sensitizers in photodynamic therapy 査読有り

Shinichiro Fuse, Keisuke Matsumura, Miori Takizawa, Shinichi Sato, Hiroyuki Nakamura,

Bioorganic and Medicinal Chemistry Letters 28 巻 ( 18 ) 頁： 3099-3104 2018年10月

The design, synthesis, and evaluation of organic dithienopyrrole-based D-π-A dyes for use as sensitizers in photodynamic therapy. 査読有り

Fuse S, Matsumura K, Takizawa M, Sato S, Nakamura H

Bioorganic & medicinal chemistry letters 28 巻 ( 18 ) 頁： 3099 - 3104 2018年10月

Rapid and Mild Synthesis of Amino Acid N-Carboxy Anhydrides: Basic-to-Acidic Flash Switching in a Microflow Reactor. 査読有り

Otake Y, Nakamura H, Fuse S

Angewandte Chemie (International ed. in English) 57 巻 ( 35 ) 頁： 11389 - 11393 2018年8月

Recent advances in the integrated micro-flow synthesis containing photochemical reactions 査読有り

Yuma Otake, Hiroyuki Nakamura, Shinichiro Fuse

Tetrahedron Letters 59 巻 ( 18 ) 頁： 1691 - 1697 2018年5月

記述言語：英語出版者・発行元：Elsevier Ltd

Micro-flow photochemical reactions have great advantage over batch photochemical reactions due to its high light-penetration efficiency. Integrated micro-flow reaction enables efficient synthesis of structurally complex compounds from simple starting materials and it can avoid handling of explosive, toxic, unstable, or odorous intermediates. Combination of micro-flow photochemical reactions with integrated micro-flow synthesis enhances their benefits. Here we summarize recently reported integrated multi-step micro-flow synthesis containing various photochemical reactions.

DOI： 10.1016/j.tetlet.2018.03.019

その他リンク： http://orcid.org/0000-0002-6836-4180

Synthesis of Pyrazolofuropyrazine via One-Pot S <inf>N</inf> Ar Reaction and Intramolecular Direct C-H Arylation 査読有り

Shinichiro Fuse, Megumi Inaba, Shinichi Sato, Manjusha Joshi, Hiroyuki Nakamura

Synthesis (Germany) 50 巻 ( 7 ) 頁： 1493 - 1498 2018年4月

掲載種別：研究論文（学術雑誌）

© Georg Thieme Verlag Stuttgart New York. Fused-ring systems containing heterocycles are attractive templates for drug discovery. Biologically active 6-5-5+6 fused-ring systems that possess heterocycles are available, but these require a relatively large number of synthetic steps for preparation. Therefore, pyrazolofuropyrazine was designed as a 6-5-5+6 ring system template that incorporates ready accessibility for drug discovery. Pyrazolofuropyrazines were successfully constructed in only a few steps via one-pot S N Ar reaction/intramolecular C-H direct arylation. As a drug candidate, pyrazolofuropyrazine has earned a favorable LogP, although significant biological activity has yet to be established; the ready accessibility of pyrazolofuropyrazine template, however, offers an opportunity for the rapid development of promising new drug candidates.

DOI： 10.1055/s-0036-1591885

その他リンク： http://orcid.org/0000-0002-6836-4180

Recent progresses in the synthesis of functionalized isoxazoles 査読有り

Taiki Morita, Somaraju Yugandar, Shinichiro Fuse, Hiroyuki Nakamura

TETRAHEDRON LETTERS 59 巻 ( 13 ) 頁： 1159 - 1171 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

Isoxazole is an important pharmacophore that is critical for biological activity. The isoxazole ring ranks 33rd in frequency among the 351 ring systems found in marketed drugs, thus suggesting a great deal of interest in the synthesis of functional isoxazoles. In recent years, various approaches have been developed for the synthesis and functionalization of isoxazoles. This comprehensive survey summarizes the recent new synthetic approaches to functionalized isoxazoles, with particular focus on the last three years with regard to the following reaction types: (1) 1,3-dipolar cycloaddition, (2) condensation, (3) cycloisomerization, and (4) direct functionalization. (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tetlet.2018.02.020

D–π–A Dyes that Contain New Hydantoin Anchoring Groups for Dye-Sensitized Solar Cells 査読有り

Hisashi Masui, Masato M. Maitani, Shinichiro Fuse, Ayaka Yamamura, Yuhei Ogomi, Shuzi Hayase, Tatsuo Kaiho, Hiroshi Tanaka, Yuji Wada, Takashi Takahashi

Asian Journal of Organic Chemistry 7 巻 ( 2 ) 頁： 458 - 464 2018年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley-VCH Verlag

The development of new anchoring groups is important to facilitate effective co-sensitization in dye-sensitized solar cells (DSSCs). Herein, stable organic D–π–A dyes that contain new heterocyclic hydantoin-based anchoring groups have been designed, synthesized, and used in DSSCs. These dye sensitizers were evaluated in terms of their absorption spectra, electrochemical properties, and performance in DSSC devices. Although only one-third of the amount of hydantoin-containing dyes adsorbed onto TiO2 relative to their cyanoacrylic-acid-containing analogues, they exhibited effective photoexcited electron-transfer properties. External quantum efficiencies of over 80 % was observed, which were comparable to those of the cyanoacrylic-acid-containing dyes. In addition, the new hydantoin-containing dyes exhibited significant robustness, which could allow improved stability of their corresponding photovoltaic devices under harsh conditions, such as high temperature and humidity.

DOI： 10.1002/ajoc.201700542

Gold(I)-Catalyzed Intramolecular SEAr Reaction: Efficient Synthesis of Isoxazole-Containing Fused Heterocycles. 査読有り

その他リンク： http://orcid.org/0000-0002-6836-4180

Morita T, Fukuhara S, Fuse S, Nakamura H

Organic letters 20 巻 ( 2 ) 頁： 433 - 436 2018年1月

Integrated Micro-Flow Synthesis Based on Photochemical Wolff Rearrangement 査読有り

Shinichiro Fuse, Yuma Otake, Hiroyuki Nakamura

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2017 巻 ( 44 ) 頁： 6466 - 6473 2017年12月

記述言語：英語出版者・発行元：WILEY-V C H VERLAG GMBH

The Wolff rearrangement of -diazo carbonyl compounds has remained important in organic synthesis since its development more than 115 years ago. The risks involved in handling diazo compounds can be minimized by utilizing micro-flow technology. In addition, photochemical Wolff rearrangement can be carried out efficiently with the aid of micro-flow technology. Integrated micro-flow synthesis is therefore well-suited to the preparation of -diazo carbonyl compounds and their photochemical Wolff rearrangement. This review article summarizes recently reported micro-flow photochemical Wolff rearrangements and their application in integrated micro-flow syntheses.

DOI： 10.1002/ejoc.201700789

Systematic Synthesis of Thiophene-based, Organic Donor-pi-Acceptor Dyes and Elucidation of Their Structure-Function Relationship 査読有り

Photodynamic therapy using a cytotoxic photosensitizer porphyrus envelope that targets the cell membrane. 査読有り

Inai M, Honda N, Hazama H, Akter S, Fuse S, Nakamura H, Nishikawa T, Kaneda Y, Awazu K

Photodiagnosis and photodynamic therapy 20 巻頁： 238 - 245 2017年12月

Shinichiro Fuse

JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 75 巻 ( 9 ) 頁： 49 - 62 2017年9月

記述言語：日本語出版者・発行元：SOC SYNTHETIC ORGANIC CHEM JPN

Thiophene-based organic D-pi-A dyes exert various functions as sensitizers of dye-sensitized solar cells, p-type semiconductors of thin-film organic solar cells, and inhibitors of aggregation of amyloid-beta and tau proteins those are regarded as promising drug targets of Alzheimer's disease. This account describes rapid and systematic synthesis of thiophene-based organic D-pi-A dyes via our developed, one-pot, cross-coupling approach and evaluation of their various functions in order to acquire high-quality structure-function relationship information.

DOI： 10.5059/yukigoseikyokaishi.75.941

Thiophene-Based Organic D-pi-A Dyes as Potent Sensitizers for Photodynamic Therapy 査読有り

Shinichiro Fuse, Miori Takizawa, Keisuke Matsumura, Shinichi Sato, Shigetoshi Okazaki, Hiroyuki Nakamura

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY ( 34 ) 頁： 5170 - 5177 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-V C H VERLAG GMBH

In this study, synthetically readily accessible, thiophene-based organic D--A sensitizers exerted high phototoxicity and are valuable as sensitizer templates for use in photodynamic therapy (PDT). Evaluation of the antitumor activity of our previously synthesized D--A sensitizers under photoirradiation revealed their potent phototoxicity. The structural requirements of the D--A sensitizer for phototoxicity were elucidated with the rapid synthesis of structurally simplified analogues and evaluation of their antitumor activity under photoirradiation. Our developed sensitizers mainly accumulated in mitochondria and damaged cancer cells through both Type I and Type II mechanisms. The developed new template could be useful in the future development of sensitizers that could fulfil the requirements for PDT.

DOI： 10.1002/ejoc.201701019

Step-by-Step Multifunctionalization of Isoxazoles Based On SEAr Reactions and C-H Direct Arylations 査読有り

Shinichiro Fuse, Taiki Morita, Hiroyuki Nakamura

SYNTHESIS-STUTTGART 49 巻 ( 11 ) 頁： 2351 - 2360 2017年6月

記述言語：英語出版者・発行元：GEORG THIEME VERLAG KG

Functionalized isoxazoles are important as pharmaceuticals and agrochemicals. Generally, electrophilic aromatic substitution or generation of carbanions/electrophilic trapping approach is used to introduce functional groups into unsubstituted heteroaromatics. However, these approaches have not been simple to apply to unsubstituted isoxazoles due to their poor nucleophilicity and instability under basic conditions. Recently several approaches have been reported to overcome these problems. This review summarizes the functionalization of isoxazoles, including SEAr reactions and C-H direct arylations, towards the step-by-step multifunctionalization of isoxazoles.

DOI： 10.1055/s-0036-1588784

Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate. 査読有り

Masui H, Yosugi S, Fuse S, Takahashi T

Beilstein journal of organic chemistry 13 巻頁： 106 - 110 2017年

Total synthesis and stereochemistry revision of mannopeptimycin aglycone 査読有り

Shinichiro Fuse, Hiroshi Tanaka, Takashi Takahashi, Takayuki Doi

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry 75 巻 ( 12 ) 頁： 1274 - 1285 2017年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Society of Synthetic Organic Chemistry

Mannopeptimycin is an attractive drug candidate due to its strong antimicrobial activity against drug-resistant strains. However, detailed elucidation of structure - activity relationship and its mode of action has been hampered because the chemical synthesis of the densely functionalized aglycone moiety consisting of cyclic hexapeptide was not established. The key point in the synthesis of the aglycone was the construction of densely functionalized unnatural amino acids, Aiha-A and Aiha-B. This account describes isolation, structural determination of mannopepti-mycins, previously reported synthesis of Aiha-A and Aiha-B as well as our short-step, high-yielding synthesis of Aihas leading to the first synthesis of mannopeptimycin aglycone with stereochemistry revision of originally proposed structure.

DOI： 10.5059/yukigoseikyokaishi.75.1274