Article
Chemistry, Applied
Jianjing Yang, Ting Zeng, Kelu Yan, Zonghui Qin, Jiangwei Wen
Summary: This study successfully developed a one-pot three-component cross-coupling reaction mediated by electrolysis, which provides a straightforward method for the synthesis of alkylthioimidazoles without the need for metal catalysts and oxidants. Water is used as the co-solvent at room temperature.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
De Chen, Hao Lu, Yuxuan Liu, Wei Deng, Renhua Qiu, Jiannan Xiang
Summary: A simple and efficient one-pot three-component cascade reaction has been developed using alpha-amino aryl ketones, indoles, and CBr4, resulting in moderate to good yields. This new strategy offers mild reaction conditions and step-economy, with easily accessible reactants and the simultaneous construction of three different new bonds (C=N, C-C, and N-Br) in a single step. The protocol developed provides a simple and practical tool for constructing diverse indole-containing heterocyclic frameworks, indicating its potential applications in medicinal and material chemistry.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Applied
Vighneshwar Shridhar Bhat, Anna Lee
Summary: A one-pot, three-component synthesis of 3-arylsulfonylated thioflavones has been developed, where the reactions were carried out without using any catalysts or additives, and the desired products were obtained through intramolecular radical cyclization. This method provides an alternative route for the synthesis of thioflavone derivatives, which have been found in various bioactive compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Jianting Ma, Xue Cui, Junyu Xu, Yinfeng Tan, Yan Wang, Xuesong Wang, Youbin Li
Summary: A one-pot strategy using ynamides as coupling reagents has been developed for the formation of alpha-keto amide bonds under extremely mild reaction conditions. Diversely structural alpha-ketoamides were obtained in up to 98% yield for 36 examples. This reaction offers practical coupling procedure, wide functional group tolerance, and extremely mild conditions, with potential applications in synthetic and medicinal chemistry.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Meng-Hui Li, Xiao-Ju Si, He Zhang, Dandan Yang, Jun-Long Niu, Mao-Ping Song
Summary: An efficient cobalt-catalyzed three-component coupling reaction is disclosed, which can construct C(sp(2))-C(sp(3)) and C-O bonds in one-pot with high yields and functional group compatibility. Mechanistic studies suggest a radical process may be involved in the reaction.
Article
Chemistry, Organic
David Philip Day, Jorge Andres Mora Vargas, Antonio Carlos Bender Burtoloso
Summary: The work presents a new method to access alpha-fluoro-alpha-triazol-1-yl ketones from sulfoxonium ylides via aazido-alpha-fluoro ketone intermediates. This approach allows modification to both reactants and has been demonstrated with 15 examples, yielding between 22% to 75%.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Ryo Hikima, Aika Takeshima, Taichi Kano
Summary: Polysubstituted furans and pyrroles were synthesized in one-pot through coupling reactions and subsequent elimination reactions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Vipin K. Pandey, Chandra Shekhar Tiwari, Arnab Rit
Summary: A silver salt-catalyzed aminophosphonylation and Strecker reaction were developed, and mechanistic studies revealed a radical pathway. This reaction system can effectively operate at room temperature without the need for solvents, ligands, or bases, and it can produce diverse products.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Olatunji S. Ojo, Alejandro Bugarin
Summary: The study presents a new one-pot synthesis method for styrene derivatives using readily available natural products, achieving regioselectivity without transition metals. The methodology has broad nucleophile scope, even accommodating sterically hindered nucleophiles.
Article
Chemistry, Organic
Jack C. Sharland, Huw M. L. Davies
Summary: Rapid access to 2,2-difluorobicyclo[1.1.1]pentanes is achieved through cyclopropanation of an α-allyldiazoacetate precursor, followed by reaction with difluorocarbene in a one-pot process. This modular synthesis method allows the preparation of previously inaccessible 2,2-difluorobicyclo[1.1.1]pentanes. Chiral 2-arylbicyclo[1.1.0]butanes also yield different products, methylene-difluorocyclobutanes, with high asymmetric induction using the same method. The modular nature of the diazo starting material allows for the rapid synthesis of larger ring systems, including bicyclo[3.1.0]hexanes.
Article
Chemistry, Organic
Alessandra Casnati, Dawid Lichosyt, Bruno Lainer, Lukas Veth, Pawel Dydio
Summary: The research presents a multicatalytic method for converting alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivity. Prochiral allylic alcohols can also be selectively transformed into different stereoisomers of the product.
Article
Chemistry, Medicinal
Tommaso Felicetti, Maria Sole Burali, Chin Piaw Gwee, Kitti Wing Ki Chan, Sylvie Alonso, Serena Massari, Stefano Sabatini, Oriana Tabarrini, Maria Letizia Barreca, Violetta Cecchetti, Subhash G. Vasudevan, Giuseppe Manfroni
Summary: A sustainable three-component reaction (3CR) was developed for synthesizing PBTZ analogues with broad-spectrum anti-flavivirus activity, with compound 22 identified as the best inhibitor in a new series. These results support PBTZ derivatives as promising anti-flavivirus agents for further development studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jiangwei Wen, Ting Zeng, Kelu Yan, Lulu Zhao, Shuyun Zhu, Jianjing Yang
Summary: A novel, straightforward, and scalable base-mediated one-pot three-component desulphurization cross-coupling strategy is reported for the synthesis of 4-cyanoimidazole derivatives. Over 35 examples are provided and achieved yields exceeding 85%. Notably, the majority of these readily available compounds can be isolated through simple filtration, thereby circumventing the need for laborious column chromatography.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Jiangwei Wen, Ting Zeng, Kelu Yan, Lulu Zhao, Shuyun Zhu, Jianjing Yang
Summary: A novel, straightforward, and scalable base-mediated one-pot three-component desulphurization cross-coupling strategy for the synthesis of 4-cyanoimidazole derivatives is reported herein. The strategy achieved yields exceeding 85% in over 35 examples, with the majority of the compounds being readily isolated through simple filtration, avoiding laborious column chromatography. The protocol demonstrated promising potential for industrial applications, showing a yield of 87% when scaled up to 10 mmol.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Naveen Diddi, Dale E. Ward
Summary: The total synthesis of dolabriferol C was achieved by a series of unique chemical reactions, simplifying the synthetic process significantly. This synthetic approach combines different stereochemical selectivities and enantioselective reactions, providing new insights for the study of related compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Shinichiro Fuse, Keiji Komuro, Yuma Otake, Hisashi Masui, Hiroyuki Nakamura
Summary: This study describes a rapid, mild, inexpensive, and less-wasteful lactamization method using highly electrophilic reagents in a microflow reactor, successfully synthesizing various lactams and cyclic peptides while suppressing undesired reactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Hiroshi Kitamura, Yuma Otake, Naoto Sugisawa, Hiroki Sugisawa, Tomonori Ida, Hiroyuki Nakamura, Shinichiro Fuse
Summary: In this study, a sequential nucleophilic substitution reaction was demonstrated in a continuous-flow reactor, where the occurrence of over nucleophilic substitution during the reaction was suppressed by the addition of imidazole. The findings suggest that the presence of imidazole significantly improves the selectivity of the reaction.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Review
Chemistry, Applied
Hisashi Masui, Shinichiro Fuse
Summary: Peptides have gained increasing importance as drugs and drug candidates. Microflow synthesis, with an inner tube diameter of <=1 mm, offers advantages such as precise control of reaction time and temperature, as well as easy scale-up. The combination of microflow technology, automated synthesis, and online monitoring has improved synthetic efficiency and provided reliable data for machine learning models.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
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
Summary: In this study, an automated continuous-flow liquid-phase peptide synthesizer was developed for the preparation of C-terminal free peptides. The synthesizer comprised an amidation unit, extraction unit, concentration unit, and control unit. The system successfully synthesized crude dipeptides and tripeptides by using a stepwise approach. The stability of the flow system was continuously monitored, and peptide synthesis was monitored using a near-infrared (NIR) sensor. This strategy enables liquid-phase continuous-flow peptide synthesis and in-line NIR monitoring of peptide-bond formation, contributing to enhanced efficiency in peptide production.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Otoka Shamoto, Keiji Komuro, Naoto Sugisawa, Ting-Ho Chen, Hiroyuki Nakamura, Shinichiro Fuse
Summary: In this study, we propose a unconventional approach to peptide cyclization using acylammonium species generated from inexpensive and less wasteful Me2NBn and ClCO(2)i-Pr. Our method shows rapid activation of the C-terminus of cyclization precursors by an acylammonium ion, enabling rapid cyclization of difficult peptides without degradation or dimerization. Compared to previous reports, our approach demonstrates superior ease of purification, productivity, and reaction mass efficiency. Furthermore, we successfully synthesized a previously reported versicotide D analogue and propose the revision of its assigned stereostructure based on our data.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Naoto Sugisawa, Kohei Nakabayashi, Hiroki Sugisawa, Shinichiro Fuse
Summary: We have developed one-step syntheses for unsymmetrical sulfamides and N-substituted sulfamate esters by modifying the nucleophile and tertiary amine. Symmetrical sulfite formation was prevented by changing the tertiary amine during the synthesis of N-substituted sulfamate esters. The impact of tertiary amines was explained using linear regression. Our approach allows for rapid production (<= 90 s) of desired products with labile acidic and/or basic groups under mild (20 degrees C) conditions, eliminating the need for tedious purification.
Review
Chemistry, Multidisciplinary
Hiroshi Kitamura, Shinichiro Fuse
Summary: PCl3 and POCl3 are important sources of phosphorus-containing compounds and have wide industrial applications. However, their high reactivity often leads to overreactions and poses significant risks. Phosphoramidites have been developed as phosphorylating reagents with mild electrophilicity, but they suffer from high costs, generation of waste, and long reaction times. Continuous-flow technology, particularly micro-flow technology, offers a promising solution by enabling precise control of reaction conditions and allowing safe operation with PCl3 and POCl3.
Article
Chemistry, Organic
Shinichiro Fuse, Ren Okabe
Summary: In this study, smaller cyclic peptides containing non-proteinogenic amino acids were synthesized in a rapid manner (60.5 min) by switching the substrate concentrations. Expensive transition-metals and coupling agents were not required. This is the first report of synthesizing smaller (≤16-membered) cyclic N-methylated peptides via a dimerization-cyclization strategy.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Naoto Sugisawa, Akira Ando, Shinichiro Fuse
Summary: Short peptides play a crucial role in drug development and the synthesis of longer peptides. Traditional methods of solid- and liquid-phase synthesis are time-consuming, expensive, and require tedious purification. In this study, we introduce a novel approach called one-flow, three-component coupling (3CC) that utilizes alpha-amino acid N-carboxy anhydrides (alpha-NCAs) as both electrophiles and nucleophiles. We successfully synthesized 17 tripeptides and achieved gram-scale synthesis of a tripeptide without the need for column chromatographic purification. By preparing alpha-NCA in situ from readily available protected amino acids, we achieved significant reductions in time and cost compared to solid-phase synthesis.
Article
Chemistry, Multidisciplinary
Hisashi Masui, Sena Kanda, Shinichiro Fuse
Summary: The authors examined previously reported preparations of (1H-indol-3-yl)methyl halides, clarified inconsistencies within the literature, and developed a highly versatile nucleophilic substitution method using microflow technologies, enabling the synthesis of various indole derivatives.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shinichiro Fuse, Sena Kanda, Hisashi Masui
Summary: Valuable indole derivatives were synthesized via the sequential 1,2-addition/nucleophilic substitution of indolyl-3-carbaldehydes. Microflow technology was used to suppress undesired reactions caused by unstable intermediates, leading to higher yields and reproducibility. The study provides a rapid and efficient method for the synthesis of structurally diverse indole derivatives.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Chemistry, Organic
Hisashi Masui, Shinichiro Fuse
Summary: Acyl ammonium cations can be prepared easily from inexpensive and commercially available nucleophilic tertiary amines and acid chlorides or chloroformates. The electrophilic nature of these cations allows rapid acylations, but also undesired reactions. The use of micro-flow technologies enables precise control over reaction time and temperature, suppressing undesired reactions and leading to more efficient and cost-effective syntheses of peptides and amino acid derivatives.
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN
(2022)
Article
Chemistry, Organic
Ren Okabe, Naoto Sugisawa, Shinichiro Fuse
Summary: This study demonstrated the rapid dual activation of an alpha-amino acid N-carboxyanhydride and alkyl chloroformate in the synthesis of a urethane-protected alpha-amino acid N-carboxyanhydride using a micro-flow reactor. The use of two amines and proper timing activation was the key to success. Various urethane-protected alpha-amino acid N-carboxyanhydrides were synthesized in high yields.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Naoto Sugisawa, Hiroki Sugisawa, Yuma Otake, Roman V. Krems, Hiroyuki Nakamura, Shinichiro Fuse
Summary: This study demonstrates a rapid and mild continuous synthesis of unsymmetrical sulfamides from sulfuryl chloride. By using a machine learning approach based on BO, high-yield reaction conditions were successfully identified.
Article
Chemistry, Organic
Shinichiro Fuse, Tsukasa Oishi, Keisuke Matsumura, Yoshihiro Hayashi, Susumu Kawauchi, Hiroyuki Nakamura
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)