Article
Chemistry, Organic
Meng-Lian Yao, Xiao-Yuan Wang, Guang-Chao Feng, Ji-Kai Liu, Bin Wu, Jin-Ming Yang
Summary: A novel palladium(II)-catalyzed intramolecular [2 + 2 + 2] annulation of indolyl 1,3-diynes is described, resulting in the synthesis of various azepino-fused carbazoles in moderate to excellent yields. The success of this transformation is attributed to the use of a carboxylic acid additive. This method exhibits broad functional group tolerance, easy handling in air, and 100% atom economy. Additionally, the scalability, late-stage derivatization, and photophysical property investigations demonstrate the potential synthetic utility of this methodology.
Article
Chemistry, Applied
Camille Van Wesemael, Nicolas Brach, Mihaela Gulea, Gaelle Blond
Summary: A series of 3-allenyl benzo[b]thiophenes were synthesized through a gold(I)-catalyzed domino reaction. The process involves a 5-endo-dig cyclization with C S bond formation and consecutive S-to-C propargyl migration via [3,3]-sigmatropic Claisen rearrangement. Various fused O-heterocycles can be obtained from a substrate bearing a 3-butynol moiety via intramolecular hydroalkoxylation. The gold-mediated 1,3-migration involving allenyl to propargyl rearrangement is also described.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Hiroki Tashiro, Masahiro Terada, Itaru Nakamura
Summary: Gold-catalyzed reactions were used to synthesize 2H-azirines with sulfenyl and acyl groups at the 3-position, yielding good to excellent results. These reactions involved internal transfer of sulfinyl oxygen atom and carbene insertion into the N-S bond for ring construction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Antonia Rinaldi, Vittoria Lange, Dina Scarpi, Ernesto G. Occhiato
Summary: In this study, the synthesis of (+/-)-epi-jungianol was successfully achieved through a gold(I)-catalyzed propargyl Claisen rearrangement/hydroarylation cascade reaction of suitably substituted propargyl vinyl ethers. Two different routes were compared, with the one involving substrates with less substitution on the vinyl moiety providing a higher overall yield despite requiring two additional steps. Additionally, a method for preparing acid-sensitive propargyl vinyl ethers with an alpha-alkyl-substituted vinyl moiety and their reactivity under gold catalysis was reported.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Rui Wu, Jiajun Lu, Tongxiang Cao, Jun Ma, Kai Chen, Shifa Zhu
Summary: An enantioselective dirhodium(II)-catalyzed cycloisomerization of diynes achieved by desymmetrization strategy provides valuable furan-fused dihydropiperidine derivatives with enantiomerically enriched alkynyl-substituted aza-quaternary stereocenter. The mechanism involving a concerted [3+2] cycloaddition/[1,2]-H shift of Rh(II) carbenoid intermediate was elucidated by DFT calculations, and weak hydrogen bondings between carboxylate ligands and alkynal were identified, which may differentiate the dirhodium(II) complex in catalyzing this transformation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Wen-Bo Shen, Ting-Ting Zhang, Meng Zhang, Jing-Jing Wu, Xiao-Lei Jiang, Guang-Xin Ru, Guang-Qin Gao, Xiu-Hong Zhu
Summary: The oxidative cyclization of diynes with pyridine N-oxides using an amide directing group is achieved with the help of catalysts such as copper and gold. Selective activation of non-polarized and aminated alkynes by these metals leads to the synthesis of a variety of pyrroles and dihydroindeno[1,2-c]pyrrol-3(2H)-ones. The difference in reactivity is suggested to be due to the multicoordinated Cu center and the linearly aligned dicoordinated Au center.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Michele Garbo, Clement Mazet
Summary: Two complementary catalytic protocols for the isomerization of stereoisomeric mixtures of vinylcyclopropanes have been presented. The use of a commercially available cationic rhodium complex leads to the synthesis of conjugated dienoates with excellent stereocontrol and high yield. By utilizing a bisphosphine ligand and a ruthenium precatalyst, cross-conjugated dienoates can be obtained through a formal 1,3-ring opening. The products show moderate to high stereoselectivity and exhibit the ability to engage in [4 + 2] cycloaddition reactions.
Article
Chemistry, Organic
Xue-Song Li, Dan-Tong Xu, Zhi-Jie Niu, Ming Li, Wei-Yu Shi, Cui-Tian Wang, Wan-Xu Wei, Yong-Min Liang
Summary: The tandem annulation of propargylic alcohols and pyridylhomopropargylic alcohols catalyzed by gold provides a atom-economical approach to a diverse set of polycyclic dihydrobenzofurans in good yields. The reaction involves 5-endo-dig cyclization/Meyer-Schuster rearrangement/Friedel-Crafts-type pathway, forming three C-C bonds and one C-O bond to give a polycyclic skeleton in a one-pot process. Additionally, the products exhibit unique optical properties, indicating their potential application value.
Review
Chemistry, Multidisciplinary
Andres Felipe Leon Rojas, Sara Helen Kyne, Philip Wai Hong Chan
Summary: Late-transition-metal-based complexes are essential catalysts in chemical synthesis, as they can rapidly and efficiently increase molecular complexity from readily accessible substrates. The control over product selectivities achieved by these catalysts, in terms of chemoselectivity, diastereoselectivity, enantioselectivity, and site-selectivity, is remarkable and has enabled a wide range of functional group transformations.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Organic
Perla Bharath Kumar, Chittala Emmaniel Raju, Patel Hinal Chandubhai, Balasubramanian Sridhar, Galla V. Karunakar
Summary: Molecules obtained from nature have various biological applications in medicinal chemistry, agrochemicals, and material sciences. Oxygen-containing molecules such as chromenes and benzochromenes are found to have potential biological applications.
Article
Chemistry, Organic
Lin Feng, Jiaxin Yao, Lin Yu, Wengui Duan
Summary: We have developed an efficient palladium-catalyzed denitrative N-arylation method, which enables the cross-coupling of N-H heteroarenes with nitroarenes. This method allows for the selective synthesis of various functionalized N-arylated heterocycles with moderate to excellent yields. Furthermore, its success in scale-up experiments and late-stage modification of natural products and pharmaceutical derivatives demonstrates the synthetic potential of this direct denitrative N-arylation protocol in synthetic chemistry.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Xin-Qi Zhu, Pan Hong, Yan-Xin Zheng, Ying-Ying Zhen, Feng-Lin Hong, Xin Lu, Long-Wu Ye
Summary: This study presents a copper-catalyzed asymmetric cyclization of alkenyl diynes involving a vinylic C(sp(2))-H functionalization, marking the first asymmetric vinylic C(sp(2))-H functionalization through cyclopentannulation. A revised mechanism involving a novel type of endocyclic copper carbene via remote-stereocontrol is proposed based on extensive mechanistic studies, providing new mechanistic insights into copper-catalyzed asymmetric diyne cyclization.
Article
Chemistry, Multidisciplinary
Akito Nakai, Tomoki Yoneda, Takayuki Tanaka, Atsuhiro Osuka
Summary: Pd-II complexation induced meso-carbon extrusion of N-fused [22]pentaphyrin(1.1.1.1.1), resulting in the formation of 22 pi aromatic compounds [22]sapphyrin. Oxidation of the compound yielded directly C-N linked dimer.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Applied
Ali Wang, Xiaoping Hu, Xin Xie, Yuanhong Liu
Summary: A gold-catalyzed cyclization/cascade skeletal rearrangement of o-cyanophenylalkynones with 3-amino-benzo[d]-isoxazoles has been developed, providing an approach for synthesizing medium-sized benzolactones. Nucleophilic attack preferentially occurs at the keto moiety instead of the gold-carbene, initiating an attractive cascade process involving carbene transfer, 1,2-aryl migration, cycloaddition, and ring-expansion resulting in multiple bonds cleavage of the initial substrates.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Yogesh Brijwashi Sharma, Debosmita Das, Murali Mohan Guru
Summary: An efficient route for the synthesis of substituted pyrazolines has been reported using readily accessible N-propargyl hydrazones. The Cu-(II) catalyst acts as a Lewis acid to form an iminium-ion intermediate via cyclization, which upon hydrolysis affords the desired pyrazolines. This methodology has been successfully applied to the synthesis of a progesterone receptor antagonist.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Takuro Matsuoka, Chihiro Motozono, Akira Hattori, Hideaki Kakeya, Sho Yamasaki, Shinya Oishi, Hiroaki Ohno, Shinsuke Inuki
Summary: The study showed that the stereocenters at the 2'- and 3'- OH groups in the ribityl tail are crucial for MAIT cell activation, while the 4'- OH group does not significantly affect the regulation of MAIT cell activity. Furthermore, it was found that 5-OP-RU forms a covalent bond to MR1 in cells within 1 hour.
Correction
Chemistry, Organic
Ayuta Yamaguchi, Shinsuke Inuki, Yusuke Tokimizu, Shinya Oishi, Hiroaki Ohno
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Takashi Kitamura, Rikito Suzuki, Shinsuke Inuki, Hiroaki Ohno, Kerry L. McPhail, Shinya Oishi
Summary: A coibamide A mimetic was designed with altered ester linkage and amino acid configurations in the macrocyclic structure, leading to the discovery of more potent derivatives. The structural-activity relationship study revealed a shared SAR with apratoxin A, suggesting a common binding site for the Tyr(Me) side chain at the luminal end of Sec61 alpha.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Luca C. C. Greiner, Norihito Arichi, Shinsuke Inuki, Hiroaki Ohno
Summary: In this study, phenyl azides substituted by an (alkylphenyl)ethynyl group were found to facilitate benzylic sp(3)(C-H) functionalization under the presence of a JohnPhosAu catalyst, resulting in the synthesis of indole-fused tetra- and pentacycles through divergent N- or C-cyclization. The chemoselectivity of the reaction was found to be influenced by the counter-anion, the electron density of the alpha-imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Atsuhito Tsuji, Takahiro Masuya, Norihito Arichi, Shinsuke Inuki, Masatoshi Murai, Hideto Miyoshi, Hiroaki Ohno
Summary: We identified a symmetric bis-sulfonamide compound, KPYC01112, as an inhibitor targeting NADH-quinone oxidoreductase. Structural modifications of KPYC01112 led to the discovery of more potent inhibitors 32 and 35. A photoaffinity labeling experiment with a newly synthesized photoreactive bis-sulfonamide revealed its binding to the subunits of complex I.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemical Research Methods
Keisuke Aoki, Asako Manabe, Hiroyuki Kimura, Yohei Katoh, Shinsuke Inuki, Hiroaki Ohno, Motohiro Nonaka, Shinya Oishi
Summary: This study investigated the preparation protocols and biological properties of mirror-image proteins (d-VHHs), which have high-affinity binding to target proteins and reduced immunogenicity. The researchers established a synthetic process for model VHHs and their mirror-image proteins and found that the mirror-image proteins showed no binding to native proteins. Additionally, it was found that d-VHHs induced significantly lower levels of antibody generation compared to native VHHs.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Takuro Matsuoka, Akira Hattori, Shinya Oishi, Mitsugu Araki, Biao Ma, Toshiki Fujii, Norihito Arichi, Yasushi Okuno, Hideaki Kakeya, Sho Yamasaki, Hiroaki Ohno, Shinsuke Inuki
Summary: This study established an MR1 presentation reporter assay system using split-luciferase, which can efficiently explore MR1 ligands. Phenylpropanoid derivatives, including coniferyl aldehyde, were identified as MR1 ligands that can inhibit the MR1-MAIT cell axis. Further investigation revealed the key structural features required for MR1 recognition. These results have significant implications for identifying a wide range of MR1 ligands and developing novel MAIT cell modulators.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Yuki Yoshida, Haruka Takeuchi, Kohei Nakagawa, Toshiki Fujii, Norihito Arichi, Shinya Oishi, Hiroaki Ohno, Shinsuke Inuki
Summary: In this study, it was found that simple biphenyl substrates derived from amino acids can participate in a radical cascade reaction under visible light irradiation in the presence of [Ir{dF(CF3)ppy}(2)(dtbpy)]PF6, enabling the direct construction of bicyclo[2.2.2]octene structures. Isotopic labeling experiments suggested that intramolecular hydrogen atom transfer is involved in the cascade processes.
Article
Chemistry, Medicinal
Rikito Suzuki, Daphne R. Mattos, Takashi Kitamura, Rina Tsujioka, Kazuya Kobayashi, Shinsuke Inuki, Hiroaki Ohno, Jane E. Ishmael, Kerry L. McPhail, Shinya Oishi
Summary: In this study, novel lysine mimetics were designed and synthesized to enhance the cytotoxicity of coibamide A (CbA), a marine cyanobacterial cyclic depsipeptide that inhibits the mammalian protein secretory pathway. The introduction of ss- and epsilon-methyl groups led to a significant increase in cytotoxicity, while retaining the ability to inhibit secretion of a model Sec61 substrate. Tandem evaluation of secretory function inhibition in living cells and cytotoxicity proved to be an effective strategy for assessing the impact of structural modifications to the linker for ring closure.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Naoya Iwamoto, Yukino Sato, Asako Manabe, Shinsuke Inuki, Hiroaki Ohno, Motohiro Nonaka, Shinya Oishi
Summary: Mirror-image proteins are a promising scaffold for drug discovery due to their high proteolytic stability and low immunogenicity. In this study, a novel variant of a monobody was designed and synthesized to facilitate the synthetic process and improve protein stability. The synthetic mirror-image protein showed good binding affinity and low immunogenicity.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Takuro Matsuoka, Akira Hattori, Shinya Oishi, Mitsugu Araki, Biao Ma, Toshiki Fujii, Norihito Arichi, Yasushi Okuno, Hideaki Kakeya, Sho Yamasaki, Hiroaki Ohno, Shinsuke Inuki
Summary: In this study, a split-luciferase assay system was established to identify MR1 ligands, including phenylpropanoid derivatives. The structure-activity relationship analysis of coniferyl aldehyde analogs revealed the key features required for MR1 recognition. These findings will contribute to the identification of a wide range of endogenous and exogenous MR1 ligands and the development of novel MAIT cell modulators.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Satoshi Suzuki, Mio Kuroda, Keisuke Aoki, Kumi Kawaji, Yoshiki Hiramatsu, Mina Sasano, Akie Nishiyama, Kazutaka Murayama, Eiichi N. Kodama, Shinya Oishi, Hironori Hayashi
Summary: The rapid development of drugs against emerging and re-emerging viruses is crucial. Researchers have designed peptide inhibitors against SARS-CoV-2 using the screening system SPICA and structures predicted by AlphaFold2.
RSC CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Shinsuke Inuki, Hitomi Tabuchi, Chiaki Matsuzaki, Yasunori Yonejima, Keiko Hisa, Ikuo Kimura, Kenji Yamamoto, Hiroaki Ohno
Summary: Exopolysaccharides (EPSs) are widely present in natural products made by bacteria, fungi, and algae, and some of them have interesting biological properties such as anticancer and immunomodulatory activities. Our recent study found that EPSs derived from Leuconostoc mesenteroides ssp. mesenteroides strain NTM048 enhanced the production of mucosal immunoglobulin A (IgA) in mice. In this study, we described the synthesis and evaluation of tetrasaccharide fragments of NTM048 EPS to gain insights into the molecular mechanism responsible for the induction of IgA.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2022)
