Article
Chemistry, Multidisciplinary
Andrea Chaves-Pouso, Andres M. Alvarez-Constantino, Martin Fananas-Mastral
Summary: In this Communication, Martin Fananas-Mastral et al. report an enantio- and diastereoselective copper-catalyzed allylboration of alkynes with allylic gem-dichlorides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Andrea Chaves-Pouso, Andres M. Alvarez-Constantino, Martin Fananas-Mastral
Summary: Allylic gem-dichlorides can be efficient substrates for catalytic asymmetric allylboration of alkynes. The method generates chiral skipped dienes with excellent levels of chemo-, regio- enantio- and diastereoselectivity, making them versatile building blocks for the synthesis of optically active compounds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Yinan Ai, Hanlin Yang, Chunying Duan, Xingwei Li, Songjie Yu
Summary: A new Co-catalyzed sequential C-C and C-F activation of gem-difluorinated cyclopropanes has been developed, allowing the formation of nucleophilic fluoroallylcobalt, followed by addition to aldehydes to yield linear (Z)- and (E)-fluorinated homoallylic alcohols. This discovery established a new strategy for the efficient transformation of gem-difluorinated cyclopropanes and synthesis of challenging fluorinated homoallylic alcohols.
Article
Chemistry, Physical
Prashant Kumar, Pravesh Kumar, Sugumar Venkataramani, S. S. V. Ramasastry
Summary: This work explores the unusual chemical reactivity pattern of allylic gem-diacetates and establishes them as new prototypes for synthesizing complex benzo[f]chromene systems. The versatility of the method in synthesizing bioactive natural products based on chromene is demonstrated, along with the discovery of interesting photochromic properties of the new classes of benzo[f]chromenes.
Article
Chemistry, Physical
Prashant Kumar, Pravesh Kumar, Sugumar Venkataramani, S. S. V. Ramasastry
Summary: This study reveals a new chemical reactivity pattern of allylic gem-diacetates and successfully synthesizes complex benzo[f]chromene compounds, demonstrating the versatility of the method. Additionally, interesting photochromic properties of the new classes of benzo[f]chromenes are discovered.
Article
Chemistry, Physical
Leiyang Lv, Huijun Qian, Anna B. Crowell, Shuming Chen, Zhiping Li
Summary: This study reports a catalytic method for controlling the selectivity of reactions, allowing access to diverse fluorinated 1,5-dienes from the same starting materials. Density functional theory calculations also revealed a ligand design for switching selectivity. This ligand-controlled approach is important for late-stage modification of complex molecules.
Review
Chemistry, Multidisciplinary
Yeosan Lee, Seungcheol Han, Seung Hwan Cho
Summary: Chemical and stereoselective transformations of polyborylalkanes are powerful methods to access optically active molecules efficiently. Gem-diborylalkanes, as versatile synthetic handles, can generate key intermediates for various enantioselective reactions. Catalytic reactions using gem-diborylalkanes can rapidly access diverse enantioenriched organoboron compounds for further transformations.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Shuai Huang, Fei-Fei Tong, Da-Chang Bai, Gao-Peng Zhang, Yang-Jie Jiang, Bo Zhang, Xuebing Leng, Ying-Long Guo, Xiao-Long Wan, Xingang Zhang, Chang-Hua Ding, Xue-Long Hou
Summary: This study presents a method for difluoroallylation of hydrazones via palladium and N-heterocyclic carbene catalysis, yielding products with high yields and selectivities. The use of chiral N-heterocyclic carbene as a ligand is crucial for enhancing selectivities and reaction productivity.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Minjae Kim, Bohyun Park, Minkyeong Shin, Suyeon Kim, Junghoon Kim, Mu-Hyun Baik, Seung Hwan Cho
Summary: A copper-catalyzed enatiotopic-group-selective allylation of gem-diborylalkanes with allyl bromides was reported in this study. The combination of copper(I) bromide and H-8-BINOL derived phosphoramidite ligand proved to be the most effective catalytic system, providing various enantioenriched homoallylic boronate esters under mild conditions. Experimental and theoretical studies elucidated the reaction mechanism and revealed the enatiotopic-group-selective trans-metalation of gem-diborylalkanes with chiral copper complex.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Leiyang Lv, Huijun Qian, Yangyang Ma, Shiqing Huang, Xiaoyu Yan, Zhiping Li
Summary: This study presents a robust Pd/NHC ligand synergistic strategy that achieves exclusive alpha-regioselectivity in the C-F bond functionalization reaction. The method enables the efficient construction of branched mono-defluorinative alkylation products.
Article
Chemistry, Organic
Xiaochen Chi, Tong Xia, Yi Yang, Tong Cao, Daopeng Zhang, Hui Liu
Summary: In this study, a novel diastereoselective synthesis strategy was reported to construct the octahydro-1H-cyclopenta[c]pyridine skeleton from (Z)-1-iodo-1,6-diene and alkyne via Pd/Au-relay catalyzed sequential intramolecular Heck-type cyclization, Sonogashira coupling, and 1,5-enyne cyclization. The strategy exhibited excellent diastereoselectivity and synthetic efficiency, and is expected to play an important role in natural product synthesis and drug development.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Sheng Cao, Chen Li, Xuan Wang, Yilei Huang, Guang Yang, Yunhao Luo, Shuanglin Qin
Summary: A robust Pd(0)-catalyzed decarboxylation alkylation has been developed using chiral tert -butanesulfinamide as the directing group, allowing for the construction of quaternary chiral centers with high diastereoselectivities and high yields at the alpha-position of chiral sulfinamides.
Article
Biochemistry & Molecular Biology
Kohei Tsuji, Kofi Baffour-Awuah Owusu, Takuya Kobayakawa, Rongyi Wang, Masayuki Fujino, Moemi Kaneko, Naoki Yamamoto, Tsutomu Murakami, Hirokazu Tamamura
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Takuya Kobayakawa, Kento Ebihara, Kohei Tsuji, Takuma Kawada, Masayuki Fujino, Yuzuna Honda, Nami Ohashi, Tsutomu Murakami, Hirokazu Tamamura
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Kohei Tsuji, Rongyi Wang, Takuya Kobayakawa, Kofi Baffour-Awuah Owusu, Masayuki Fujino, Moemi Kaneko, Naoki Yamamoto, Tsutomu Murakami, Hirokazu Tamamura
Summary: Several potential anti-HIV agents have been identified based on fragment peptides libraries containing octa-arginyl residues that cover the whole sequence of an HIV-1 capsid protein. Derivatives of potent CA-19L peptide overlapping with the Helix 9 region of the CA protein were synthesized, showing promising anti-HIV activity. These new compounds may provide valuable insights into the functions of CA proteins.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Takuya Kobayakawa, Kohei Tsuji, Kiju Konno, Ai Himeno, Ami Masuda, Tingting Yang, Kohei Takahashi, Yusuke Ishida, Nami Ohashi, Takeo Kuwata, Kaho Matsumoto, Kazuhisa Yoshimura, Hiromi Sakawaki, Tomoyuki Miura, Shigeyoshi Harada, Shuzo Matsushita, Hirokazu Tamamura
Summary: The study synthesized hybrid molecules of CD4 mimics and found that modification with a PEG unit was more suitable than a long alkyl chain, showing higher anti-HIV activity and lower cytotoxicity. In a rhesus macaque pharmacokinetics study, the hybrid compound had a better PK profile, with intramuscular injection being more effective than intravenous injection to maintain high blood concentration of the CD4 mimic.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Sayaka Boku, Miyuki Nakayama, Moemi Kaneko, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: A small molecule designed to mimic hydrophobic interactions between HIV-1 capsid proteins has shown significant anti-HIV-1 activity. Structure activity relationship (SAR) studies of its derivatives provide valuable information for the design and development of novel anti-HIV agents targeting the capsid protein. This new drug has the potential to be an effective treatment for HIV in the future.
Article
Chemistry, Organic
Takuya Kobayakawa, Chika Azuma, Yuki Watanabe, Shunsuke Sawamura, Atsuhiko Taniguchi, Yoshio Hayashi, Kohei Tsuji, Hirokazu Tamamura
Summary: This study reports improved methods for convergent synthesis using a chloroalkene dipeptide isostere (CADI), demonstrating the direct application of Fmoc-protected CADI in solid-phase peptide synthesis and the discovery of a CADI-containing peptidomimetic with superior inhibitory effects on amyloid-beta aggregation compared to the parent peptide.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Microbiology
Kouki Matsuda, Takuya Kobayakawa, Ryusho Kariya, Kiyoto Tsuchiya, Shoraku Ryu, Kohei Tsuji, Takahiro Ishii, Hiroyuki Gatanaga, Kazuhisa Yoshimura, Seiji Okada, Akinobu Hamada, Hiroaki Mitsuya, Hirokazu Tamamura, Kenji Maeda
Summary: A drug called YSE028 has been found to reverse the latency of HIV-1 in latently infected cells, with enhanced efficacy when used in combination with JQ1. Furthermore, this drug can induce apoptosis in HIV-1 latently infected cells and shows minimal toxicity in vitro and in vivo.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kohei Tsuji, Takuya Kobayakawa, Kiju Konno, Ami Masuda, Kohei Takahashi, Nami Ohashi, Kazuhisa Yoshimura, Takeo Kuwata, Shuzo Matsushita, Shigeyoshi Harada, Hirokazu Tamamura
Summary: Researchers have developed small molecule CD4 mimics with excellent aqueous solubility and anti-HIV activity, laying the foundation for future design of CD4 mimic molecules.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Haruki Kitamura, Sayaka Sukegawa, Kouki Matsuda, Kousuke Tanimoto, Takuya Kobayakawa, Kazuho Takahashi, Hirokazu Tamamura, Kiyoto Tsuchiya, Hiroyuki Gatanaga, Kenji Maeda, Hiroaki Takeuchi
Summary: Combinational antiretroviral therapy (cART) successfully suppresses viral load but fails to eliminate HIV-1 reservoirs. "Shock and Kill" strategy using latently-reversing agents (LRAs) is being developed to reactivate latent HIV-1 and induce cell death. This study identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate that effectively reactivated HIV-1 and induced cell death in latently-infected cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Rongyi Wang, Kohei Tsuji, Takuya Kobayakawa, Yishan Liu, Kazuhisa Yoshimura, Shuzo Matsushita, Shigeyoshi Harada, Hirokazu Tamamura
Summary: This study developed hybrid molecules containing small CD4 mimics and gp41-C-terminal heptad repeat-related peptides, and compared the efficacy of different synthesis methods. The results showed that these hybrid molecules have dual targets and significantly inhibit HIV activity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Takuya Kobayakawa, Masaru Yokoyama, Kohei Tsuji, Masayuki Fujino, Masaki Kurakami, Takato Onishi, Sayaka Boku, Takahiro Ishii, Yutaro Miura, Kouki Shinohara, Yuki Kishihara, Nami Ohashi, Osamu Kotani, Tsutomu Murakami, Hironori Sato, Hirokazu Tamamura
Summary: The HIV-1 capsid is crucial for viral replication and represents a potential target for antiviral drugs. A small molecule designed to mimic the interaction between CA proteins has shown significant anti-HIV-1 activity. In this study, molecules with different structures based on this small molecule were synthesized and found to have significant anti-HIV activity, with advantages over previous compounds.
Article
Multidisciplinary Sciences
Nobuyo Higashi-Kuwata, Kohei Tsuji, Hironori Hayashi, Haydar Bulut, Maki Kiso, Masaki Imai, Hiromi Ogata-Aoki, Takahiro Ishii, Takuya Kobayakawa, Kenta Nakano, Nobutoki Takamune, Naoki Kishimoto, Shin-ichiro Hattori, Debananda Das, Yukari Uemura, Yosuke Shimizu, Manabu Aoki, Kazuya Hasegawa, Satoshi Suzuki, Akie Nishiyama, Junji Saruwatari, Yukiko Shimizu, Yoshikazu Sukenaga, Yuki Takamatsu, Kiyoto Tsuchiya, Kenji Maeda, Kazuhisa Yoshimura, Shun Iida, Seiya Ozono, Tadaki Suzuki, Tadashi Okamura, Shogo Misumi, Yoshihiro Kawaoka, Hirokazu Tamamura, Hiroaki Mitsuya
Summary: COVID-19 caused by SARS-CoV-2 remains a serious threat to global public health. This study identifies two orally available small molecules, TKB245 and TKB248, that specifically inhibit the enzymatic activity of the main protease (M-pro) of SARS-CoV-2, showing significantly more potency in blocking the infectivity and replication of various SARS-CoV-2 strains compared to other available therapeutics.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Kohei Tsuji, Kofi Baffour-Awuah Owusu, Yutaro Miura, Takahiro Ishii, Kouki Shinohara, Takuya Kobayakawa, Akino Emi, Takashi Nakano, Youichi Suzuki, Hirokazu Tamamura
Summary: Membrane fusion is a crucial step in the replication cycles of SARS-CoV-2 and HIV-1. Researchers have developed potent fusion inhibitors for SARS-CoV-2 and HIV-1 based on specific peptide sequences. This study reports the development of dimerized HR2 peptides for SARS-CoV-2, which exhibit significantly higher antiviral activity compared to monomers, suggesting a potential strategy for designing effective inhibitors for SARS-CoV-2.
Article
Chemistry, Organic
Kohei Tsuji, Takahiro Ishii, Takuya Kobayakawa, Nami Ohashi, Wataru Nomura, Hirokazu Tamamura
Summary: Protein kinase C (PKC) is associated with various diseases such as cancer and Alzheimer's disease and is a target for treatment. Researchers have developed an improved FRET-based assay to find effective PKC ligands, which has increased sensitivity and detection accuracy.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Organic
Takuya Kobayakawa, Hikaru Takano, Takahiro Ishii, Kohei Tsuji, Nami Ohashi, Wataru Nomura, Toshiaki Furuta, Hirokazu Tamamura
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)
