Article
Chemistry, Multidisciplinary
Jian Pan, Qingwen Tan, Saibin Zhu, Xiaohui Yan, Yu Li, Zhoukang Zhuang, Xiangcheng Zhu, Yanwen Duan, Yong Huang
Summary: The identification and characterization of enediyne polyketide synthases (PKSEs) have revealed that polyene is a common intermediate produced by PKSEs, but the pathway for formation of enediyne cores remains unclear. In this study, we report the biosynthesis of pentaene polyols and cinnamic acid derivatives from an activated enediyne biosynthetic gene cluster. We found that increasing the cellular pool of (L)-Phe improved the yields of polyene polyols, and a flexible ammonia lyase was responsible for biosynthesis of cinnamic acid derivatives. Our findings also suggest a possible role of a polyene epoxide intermediate in the construction of 9-membered enediyne macrocycles.
Article
Chemistry, Multidisciplinary
Xin-Xin Yang, Ming-Ying Wu, Shao-Qiu Wang, Shang-Dong Yang
Summary: This study reports a transition-metal-catalyzed reaction that allows for the direct functionalization of insert C-H bonds to form carbon-carbon bonds. The reaction proceeds via a unique eight-membered palladacyclic intermediate and demonstrates good compatibility with various functional groups under mild reaction conditions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Tetsu Tsubogo, Fumiya Okamura, Akiho Omori, Hiromi Uchiro
Summary: In this study, a method for synthesizing eight-membered cyclic ethers through direct C-O bond connection using intramolecular Ullmann coupling reaction was reported. The use of a strongly coordinating 4-pyrrolidinopyridine ligand was found to accelerate the reaction rate and facilitate the synthesis of allelopathically active heliannuol A. This approach bypasses protection and deprotection steps, offering a new strategy for the synthesis of benzannulated eight-membered ring structures.
Article
Agriculture, Multidisciplinary
Shilu Deng, Jing Li, Ting Luo, Zeyuan Deng
Summary: The flax cyclic peptide (CLA) in flaxseed oil (FSO) has been found to improve the antioxidant stability of FSO and inhibit metal ions-induced oxidation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Peng-Bo Bai, Ming-Ying Wu, Xin-Xin Yang, Gang-Wei Wang, Shang-Dong Yang
Summary: Here, we present the first atroposelective acyloxylation of a C(sp2)-H bond using a phosphine oxide directing group. Surprisingly, this reaction proceeds via an eight-membered palladacycle intermediate instead of the more favored five-membered palladacycle. Additionally, we found that L-pGlu-OH, a readily available chiral amino acid derivative, is the best chiral ligand for promoting this atroposelective remote C-H functionalization reaction.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Organic
Tomohiro Fujino, Tadashi Hyodo, Yuko Otani, Kentaro Yamaguchi, Tomohiko Ohwada
Summary: This study discovered the rarity of neighboring group participation involving a 6-membered ring structure in organic chemistry and confirmed the existence and role of this intermediate in the syn-migration of peri-ester indanone oximes.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Xiongda Xie, Ming Bao, Kewei Chen, Xinfang Xu, Wenhao Hu
Summary: A dirhodium and chiral phosphoric acid co-catalyzed asymmetric three-component reaction was developed for the synthesis of chiral dibenzoazepine analogues. This reaction involves the interception of a transient oxonium ylide and reacts with a diazo compound, an alcohol, and a seven-membered imine to produce the desired products in good yields with excellent stereoselectivity. The generated products can be further converted to enantioenriched tetracyclic frameworks with embedded functional groups.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Prabuddha Bhattacharya, Soham Chakraborty, Ashwin Balaji, Amit Basak
Summary: This study investigates the kinetics of Bergman cyclization reaction and finds that the structural features of enediynes affect their reaction rates. The cd-distance model and the transition state model are proposed based on the analysis of experimental data. Recently, a distortion model is introduced to explain the regioselectivity of nucleophilic addition to unsymmetrical enediynes. The study also reveals that larger interior angles at the proximal alkyne carbons in enediynes lead to lower activation barriers and faster reaction rates.
Article
Chemistry, Multidisciplinary
Angelica Mejia Fajardo, Nicolas Queyriaux, Aurele Camy, Laure Vendier, Mary Grellier, Iker Del Rosal, Laurent Maron, Sebastien Bontemps
Summary: This study demonstrates the successful activation of the carbonyl function of five different benzaldehyde derivatives using a masked form of OBB intermediate, and the characterization and analysis of the resulting compounds through various experimental methods.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Physical
Matthew G. Christianson, Anna C. Doner, Matthew M. Davis, Alanna L. Koritzke, Justin M. Turney, Henry F. Schaefer, Leonid Sheps, David L. Osborn, Craig A. Taatjes, Brandon Rotavera
Summary: Ethyloxirane is a cyclic ether produced during combustion processes, and its consumption pathways are complex, potentially requiring an expansion of submechanisms to increase the fidelity of chemical kinetics mechanisms.
INTERNATIONAL JOURNAL OF CHEMICAL KINETICS
(2021)
Article
Chemistry, Multidisciplinary
Lars Denker, Bartosz Trzaskowski, Rene Frank
Summary: The study introduces cyclic five-membered triel(i) carbenoides E(AmIm) for E = Ga, In, Tl, bridging the gap between four- and six-membered triel(i) carbenoides supported by HGiso and HNacNac. Ga(AmIm) is found to act as a strong sigma-donor ligand in transition metal complexes, and the intermediacy of Al(i) carbenoide Al(AmIm) is rationalized based on the isolation of an Al(iii) insertion product.
CHEMICAL COMMUNICATIONS
(2021)
Article
Electrochemistry
Tutku Mutlu, Rezan Demir-Cakan
Summary: Li-Se batteries are considered as one of the most promising battery systems for future energy storage needs. The study shows that carbonate-based electrolytes can be simply employed in the field of Li-Se batteries, which provides a cost-effective and feasible option.
ELECTROCHIMICA ACTA
(2021)
Article
Chemistry, Organic
Akihiro Sugawara, Hirokazu Takada, Tomoyasu Hirose, Aoi Kimishima, Takeshi Yamada, Masaki Toda, Toru Kojima, Takanori Matsumaru, Toshiaki Sunazuka
Summary: A highly efficient Pd-catalyzed hydrostannylation method for alkyl ethynyl ethers has been developed, allowing for the generation of alkenyl ethers with high regio- and stereoselectivity. This method also enables scalable synthesis and construction of the core framework of luminamicin, containing all functional groups and stereocenters.
Article
Chemistry, Analytical
Alexey A. Bogdanov, Sergey Panin, Pavel S. Lyubutin, Alexander Eremin, Dmitry G. Buslovich, Anton Byakov
Summary: This study designs an automated laboratory facility based on a servo-hydraulic testing machine to estimate parameters of mechanical hysteresis loops using the digital image correlation (DIC) method. The testing facility is described, and the calculation methods for elastic modulus, offset yield strength (OYS), and parameters of mechanical hysteresis are presented. The results show that the damage accumulation in the fatigue process of neat polyimide (PI) is accompanied by a decrease in loop areas, and failure occurs when the loop areas decrease by at least about 5 kJ/m(3). It is revealed that fractography data, such as the pattern and sizes of fatigue crack initiation and propagation zones, do not correlate well with the parameters of hysteresis loops.
Article
Oncology
Yong-Fa Zhang, Ming Shi, Liang-He Lu, Lu Wang, Rong-Ping Guo
Summary: The study found that the Hong Kong Liver Cancer (HKLC) staging system is consistently the best prognostic model in patients with intermediate stage hepatocellular carcinoma (HCC), which can help improve the design of future clinical trials.
JOURNAL OF HEPATOCELLULAR CARCINOMA
(2021)
Article
Chemistry, Multidisciplinary
Yuma Otake, Yusuke Shibata, Yoshihiro Hayashi, Susumu Kawauchi, Hiroyuki Nakamura, Shinichiro Fuse
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
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.
