Article
Chemistry, Multidisciplinary
Mu-Peng Luo, Yi-Jie Gu, Shou-Guo Wang
Summary: A highly efficient enantioselective direct C-H functionalization of beta-carbolines via a Minisci-type radical process has been disclosed. This protocol allows the construction of C1 aminoalkylated beta-carbolines directly with high levels of enantioselectivities from readily available substrates. The developed method has been utilized as a highly efficient synthetic strategy for the concise asymmetric total synthesis of marine alkaloids.
Article
Chemistry, Organic
Nojus Cironis, Kang Yuan, Stephen P. Thomas, Michael J. Ingleson
Summary: A simple and regioselective synthesis of di-indole sulfides was achieved by electrophilic aromatic substitution of the C3-position of indoles using Xtalfluor-E as the sulfenylating reagent. The addition of amine bases had a significant effect on the reaction outcome, and Hunigs base was found to be the optimal base for high yield. This is the first report utilizing Xtalfluor-E in electrophilic aromatic substitution to form C-S bonds and the method is applicable to a wide range of functionalized indoles without N1-protection.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
In-Soo Myeong, Nadide Hazal Avci, Mohammad Movassaghi
Summary: The first total synthesis of (-)-kopsifoline A and (+)-kopsifoline E was achieved in this study, featuring a biogenetically inspired regioselective C17-functionalization strategy for a versatile intermediate. The vinylogous urethane substructure of the intermediate allowed for the synthesis of (-)-kopsifoline D via C3-C21 bond formation under Mitsunobu reaction conditions, as well as selective C17-functionalization en route to (-)-kopsifoline A and (+)-kopsifoline E.
Article
Chemistry, Organic
Akira Kabuki, Junichiro Yamaguchi
Summary: The dictyodendrins, marine alkaloids with a unique core structure, were successfully synthesized by utilizing a previously developed method and two C-H functionalization steps.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Zhenrong Liu, Zhiqiang Wang, Haiyan Liao, Zheng Li
Summary: An efficient method for constructing 1,2,3-triarylindoles through one-pot multicomponent reactions using calcium carbide, 3mol of iodoarenes, and aromatic amines as starting materials was described. This method allows for the simultaneous formation of five bonds in one step, resulting in a series of target products. The main advantages of this protocol include the use of a convenient alkyne source, a wide scope of substrates, and a simple workup procedure. The method can also be scaled up to gram scale.
Article
Chemistry, Organic
Tetsuhiro Nemoto
Summary: This paper presents the advances in the synthesis of dragmacidin E, a bis-indole alkaloid isolated from a deep-water marine sponge in southern Australia. Synthetic studies conducted by the Funk, Feldman, Jia, and Nemoto groups are summarized, including the total synthesis of (±)-dragmacidin E achieved by Feldman et al. in 2011.
TETRAHEDRON LETTERS
(2023)
Article
Chemistry, Medicinal
Gangqiang Yang, Hao Xie, Conghui Wang, Chen Zhang, Liping Yu, Luyu Zhang, Xin Liu, Ruoxuan Xu, Zhihua Song, Rongxia Liu, Minoru Ueda
Summary: In this study, a series of novel Eudistomin Y fluorescent derivatives were designed and synthesized, and structure-activity relationships analysis showed that a quarter of the derivatives exhibited higher potency against cancer cell proliferation than the original Eudistomin Y1. Among them, derivative H1k showed robust antiproliferative activity against MDA-MB-231 cells by inhibiting lysosomes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ganapathy Ranjani, Rajagopal Nagarajan
Summary: A novel metal-free cross-dehydrogenative coupling method was developed, leading to the synthesis of a series of specific compounds with controlled functional groups. High yields were achieved through precise control of reaction conditions, offering a new strategy in the field of organic synthesis.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Wei Cao, Yingchao Dou, Cyrille Kouklovsky, Guillaume Vincent
Summary: The first total synthesis of the monoterpene indole alkaloids ophiorrhine A is reported via a late stage bioinspired intramolecular Diels-Alder cycloaddition. The synthesis includes the construction of the indolopyridone moiety, cyclodehydration, and the desired spontaneous intramolecular Diels-Alder cycloaddition.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Xu-Yang Hu, Hai-Feng Xu, Qiang Chen, You-Lu Pan, Jian-Zhong Chen
Summary: In this study, a novel synthesis method was developed for the indolo[2,1-alpha]isoquinoline core structure under air environment, resulting in the successful synthesis of various valuable derivatives with good yields. A radical pathway was proposed to explain the experimental results.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Plant Sciences
Yuka Maeyama, Yuta Nakashima, Hikaru Kato, Yuki Hitora, Kazuhiko Maki, Natsumi Inada, Shunya Murakami, Tomoaki Inazumi, Yuji Ise, Yukihiko Sugimoto, Hayato Ishikawa, Sachiko Tsukamoto
Summary: Amakusamine (1), a simple methylenedioxy dibromoindole alkaloid, was isolated from a marine sponge of the genus Psammocinia. It was found that compound 1 could inhibit the formation of multinuclear osteoclasts induced by RANKL, with an IC50 value of 10.5 µM. The structure-activity relationship of compound 1 was also investigated through synthetic derivatives.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Multidisciplinary
Minakshi Altia, Pazhamalai Anbarasan
Summary: An efficient and general method has been developed for the synthesis of 2- and 3-acylindoles with high regioselectivity from o-acylanilines and alpha-hydroxycarbonyl compounds. The method involves the intramolecular trapping of an in situ generated aminoenol intermediate and an interrupted Heyns rearrangement pathway, followed by aromatization or rearrangement/aromatization. Important features of this method include excellent regiocontrol, good functional group tolerance, operational simplicity, and applicability to gram-scale synthesis and the synthesis of an anti-tumor agent.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Kosuke Okada, Ken-ichi Ojima, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: The synthesis of (+)-pleiocarpamine, (+)-voacalgine A and (+)-bipleiophylline was achieved in this study. The 10-step synthesis of (+)-pleiocarpamine features the construction of stereochemistry at the C16 position by radical cyclization and the synthesis of the highly strained cage-like structure via Pd-catalyzed intramolecular aromatic C-H functionalization. By modifying the biomimetic aerobic oxidative coupling of tryptophane derivatives catalyzed by FePc(CO2H)(8), the oxidative coupling of (+)-pleiocarpamine with pyrocatechuic acid produced (+)-voacalgine A. The total synthesis of (+)-bipleiophylline was completed by the second coupling of (+)-voacalgine A with (+)-pleiocarpamine or the one-pot couplings of 2 equiv of (+)-pleiocarpamine with pyrocatechuic acid.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Yuping Xiong, Feihua Du, Linghui Zeng, Zhiyuan Chen
Summary: Herein, we present a catalytic system of I2/PhI(OAc)2 for the pragmatic construction of C-N bonds through C-H/N-H oxidative coupling protocol. Divergent pyrrolo[2,3-b]indoles were efficiently prepared via I2-catalyzed intramolecular C-H amination reactions from (E/Z)-2-indolylenamines under metal-free conditions. The resulting pyrrolo[2,3-b]indoles were obtained with mostly good to excellent yields, tolerating various functional groups under mild reaction conditions. Notably, both the (E) and (Z) isomers of the starting materials were efficiently transformed into the targeted product. The I+-mediated catalytic cycle was proposed based on mechanistic studies for this reaction.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Haruka Kawakam, Naoto Chatan
Summary: The reaction between N-pyrimidinyl aniline derivatives and internal alkynes in the presence of a catalytic amount of Ni(0) complex leads to the alkyne annulation of C-F/N-H, resulting in the formation of indole derivatives. The activation of the C-F bond, a crucial step in this reaction, is facilitated by a pyrimidine directing group. The use of a base, such as NaH, is necessary for the completion of the reaction.
Review
Chemistry, Multidisciplinary
Satoshi Yokoshima
Summary: This highlight review summarizes the syntheses of 2-azabicyclo-[3.3.1]nonanes, focusing on sarain A and madangamines. Researchers used unique strategies to construct different structures with additional substituents and functional groups in the target molecule.
Article
Chemistry, Multidisciplinary
Yuan Jin, Kensuke Orihara, Fumiki Kawagishi, Tatsuya Toma, Tohru Fukuyama, Satoshi Yokoshima
Summary: The total synthesis of Haliclonin A was achieved through a series of reactions including Birch reduction/alkylation, ring-closing metathesis, intramolecular cyclopropanation, and stereoselective 1,4-addition, leading to the formation of the desired compound.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Ryosuke Kori, Keigo Murakami, Yoshitake Nishiyama, Tatsuya Toma, Satoshi Yokoshima
Summary: The study reveals the mechanism of copper-mediated reaction for the formation of nitriles, involving iodoalkyne and iodotriazole as intermediates.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2021)
Review
Chemistry, Medicinal
Hidetoshi Tokuyama
Summary: This study presents a benzyne-mediated cyclization/functionalization protocol for highly substituted benzene derivatives fused with N-heterocyclic rings, allowing the synthesis of various alkaloids.
CHEMICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Chemistry, Organic
Takahiro Noro, Juri Sakata, Hidetoshi Tokuyama
Summary: This paper describes the synthetic studies of a discorhabdin alkaloid with C2-N18 bond, which includes A-F hexa-cyclic framework. The specific bond was formed by Mitsunobu reaction, and later a tricyclic o-quinone intermediate was obtained through an aerobic oxidative cascade cyclization. In the later stage of the synthesis, complex ring systems were constructed using intramolecular Heck cyclization of the halogenated tricyclic o-quinone.
TETRAHEDRON LETTERS
(2021)
Editorial Material
Chemistry, Organic
Hidetoshi Tokuyama
JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN
(2022)
Article
Chemistry, Organic
Haoran Xiong, Kei Yoshida, Kosuke Okada, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: This study presents a novel chiral catalytic system for the enantioselective 5-endo-trig bromocycloetherification, delivering high yields and enantioselectivity. The results indicate that the structure of the catalyst plays a crucial role in determining the selectivity of the products.
TETRAHEDRON LETTERS
(2022)
Article
Chemistry, Applied
Masatoshi Yamada, Kazuki Azuma, Iori Takizawa, Yuki Ejima, Mitsuhisa Yamano, Kimio Satoh, Takayuki Doi, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: A scalable asymmetric total synthesis of (-)-emetine, an important component in emetics, has been achieved. The synthesis involved 13 steps of highly efficient chemical reactions, including catalytic asymmetric allylation and industrial deoxygenation, eliminating the need for chromatographic purification. A high yield of (-)-emetine center dot 2HCl (12%) with over 93.2% HPLC purity was obtained, and the synthesis can be easily scaled up for larger production and currently used in natural ipecac syrup for clinical application.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Multidisciplinary
Hirofumi Ueda, Soichiro Sato, Kenta Noda, Hiroyuki Hakamata, Eunsang Kwon, Nagao Kobayashi, Hidetoshi Tokuyama
Summary: A biomimetic oxidative dimerization method for tryptophan derivatives was developed using oxygen as a bulk oxidant in aqueous media catalyzed by an iron octacarboxy phthalocyanine complex. The highly active iron catalyst enables aerobic enzyme-mimetic oxidation in a flask. This method provides a facile access to a broad range of dimerized peptides with unique scaffold, which can be used as a powerful tool for creating new small- and medium-sized molecules as drug candidates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ken-ichi Ojima, Hirofumi Ueda, Hidetoshi Tokuyama, M. Iyag
Summary: This study conducted synthetic studies on a dimeric indole alkaloid, cimicidu-phytine, by modifying the synthesis of (+)-haplophytine. The key aspects of this synthesis included the chemoselective deallylation of an N,O-diallyl derivative of a hydroxy aniline and the copper sulfate-mediated oxidative lactonization via oxidation of the amino moiety. A highly convergent strategy successfully synthesized the originally proposed cimiciduphytine, but it proved to be unstable under air and underwent cyclization to generate a bridged derivative.
BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN
(2023)
Article
Chemistry, Multidisciplinary
Kosuke Okada, Ken-ichi Ojima, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: The synthesis of (+)-pleiocarpamine, (+)-voacalgine A and (+)-bipleiophylline was achieved in this study. The 10-step synthesis of (+)-pleiocarpamine features the construction of stereochemistry at the C16 position by radical cyclization and the synthesis of the highly strained cage-like structure via Pd-catalyzed intramolecular aromatic C-H functionalization. By modifying the biomimetic aerobic oxidative coupling of tryptophane derivatives catalyzed by FePc(CO2H)(8), the oxidative coupling of (+)-pleiocarpamine with pyrocatechuic acid produced (+)-voacalgine A. The total synthesis of (+)-bipleiophylline was completed by the second coupling of (+)-voacalgine A with (+)-pleiocarpamine or the one-pot couplings of 2 equiv of (+)-pleiocarpamine with pyrocatechuic acid.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Yuko Wakahara, Takahiro Noro, Juri Sakata, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: This study investigates the construction of tetrahydroquinolines with a spirocyclic structure at the 4-position. A five-step sequence was developed, including the synthesis of benzocyclopentanone oxime, followed by the addition of aryl Grignard Reagent, intramolecular Friedel-Crafts acylation, condensation with hydroxylamine, and reductive ring expansion reaction. The method was successfully used to construct various tetrahydroquinolines with spirocyclic rings of different sizes and adamantane and indane structures at the 4-position.
Article
Chemistry, Organic
Kosuke Okada, Hirofumi Ueda, Hidetoshi Tokuyama
Summary: The total synthesis of (+/-)-vinoxine was achieved using Tf2O-mediated Bischler-Napieralski reaction, assembling a multi-substituted tetrahydropyrido[1,2-a]indole skeleton. The characteristic diazabicyclo[3.3.1]nonane skeleton was stereoselectively constructed via radical cyclization based on the stereochemistry of the C3 position. This methodology opens up new options for synthesizing natural products and pharmaceuticals containing the multi-substituted pyrido[1,2-a]indole skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Kohta Ide, Miyu Furuta, Hidetoshi Tokuyama
Summary: A mild photoredox-catalyzed intramolecular cyclopropanation of alkenes with alpha-bromo-beta-keto esters in an aqueous medium was developed. The reaction proceeds in one-pot under exceptionally mild conditions at room temperature, yielding a wide range of functionalized bicyclic cyclopropanes. A broad range of substrates consisting of various alkenes and both base- and acid-sensitive functionalized esters were feasible under the reaction conditions.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tomoko Shiobara, Yoko Nagumo, Rie Nakajima, Tohru Fukuyama, Satoshi Yokoshima, Takeo Usui
Summary: Mersicarpine can reversibly arrest the cell cycle progression in S-phase and induce apoptosis in human leukemia cell line HL60. It also inhibits protein synthesis, making it a novel translation inhibitor.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2021)
