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