Article
Chemistry, Multidisciplinary
Rina Mahato, Chinmoy Kumar Hazra
Summary: In this study, pentafluorophenol was revealed as an effective catalyst for the synthesis of (spirocyclic) tetrahydro-beta-carbolines via the Pictet-Spengler reaction. This straightforward catalytic system operates under mild conditions, yielding indole alkaloids in excellent yield and exhibiting remarkable functional group tolerance, including late-stage modifications. This transformation provides a practical and adaptable approach for the gram-scale synthesis of the natural alkaloid Komavine and enables the synthesis of the commercial drug Tadalafil.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Arka Das, Christine Jonathan, Rana Saha, Md Imran Ahmed, Subhendu Bhowmik
Summary: A regioselective decarboxylative alkynylation of tetrahydro-beta-carboline-1-carboxylic acid under peroxide-free condition is reported, which exhibits high selectivity for the 1-position of tetrahydro-beta-carboline. Depending on the reagent, the reaction can produce alkynylated or enaminone products. The reaction proceeds through sequential decarboxylative iminium ion formation followed by an alkynylation and oxidative rearrangement cascade.
Article
Chemistry, Organic
Fan Xiao, Shi-Ming Xu, Xiu-Qin Dong, Chun-Jiang Wang
Summary: The Ir-catalyzed asymmetric tandem allylation/iso-Pictet-Spengler cyclization reaction provides a direct and practical approach for accessing tetrahydro-gamma-carboline derivatives with multiple functional groups and stereogenic centers in good to high yields and excellent stereoselective control. The wide substrate generality, easily available substrates, and simple chiral catalytic system demonstrate the great potential practicality of this efficient protocol.
Article
Chemistry, Multidisciplinary
Yogesh Brijwashi Sharma, Rajveer Singh, Chetan Paul Singh, Yogesh P. Bharitkar, Abhijit Hazra
Summary: In this study, a one-step synthesis of tetrahydro-beta-carbolino-spiroindolone/spiroacenapthylene scaffold from tryptamine and isatin was achieved using lemon juice as a biocatalyst system via Pictet-Spengler Reaction. The reaction provided clean and convenient synthesis of spiroindolones. The product was separated and characterized using chromatographic and spectroscopic techniques. Bio evaluation showed promising activity against several cancer cell lines for specific compounds.
Article
Chemistry, Multidisciplinary
Haiting Yin, Qin Ma, Yushan Wang, Xiaoxia Gu, Zhijun Feng, Yunjun Wu, Ming Wang, Shaoyin Wang
Summary: The study presents a facile and efficient route to tetrahydro-beta-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative annulation reactions. The reaction involves a cascade sequence of Friedel-Crafts-type alkylation followed by intramolecular Click reaction, forming multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.
Article
Chemistry, Medicinal
Ramil Y. Baiazitov, Hongyan Qi, Tamil Arasu, William Lennox, Liangxian Cao, Marla Weetall, Bansri Furia, Jin Zhuo, Soongyu Choi, Min Jung Kim, Josephine Sheedy, Thomas Davis, Young-Choon Moon
Summary: This paper describes a lead optimization campaign that led to the discovery of Emvododstat (PTC299), a highly potent DHODH inhibitor. Modulating the activity of this enzyme can be used to control diseases associated with rapid, out-of-control cell growth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Zhihui Shao, Xiaoyu Zhang, Xinyan Li, Weilin Wang, Jiaqiao Ding, Bing Cui, Mingqin Zhao
Summary: An efficient and green method for the synthesis of tetrahydro-beta-carbolines using a dehydrogenative coupling reaction between alcohols and tryptamines is reported. The reaction proceeds under mild conditions with the presence of a catalytic amount of (PNP)-P-iPr Mn catalyst and a weak base (Na2CO3). This strategy shows good tolerance towards various benzylic and aliphatic alcohol substrates with different functional groups, leading to diverse products in good to excellent yields.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Jay Prakash Soni, Manda Sathish, Fabiane M. Nachtigall, Leonardo S. Santos, Nagula Shankaraiah
Summary: The Pictet-Spengler reaction is an efficient synthetic tool for constructing tetrahydro-beta-carbolines and tetrahydroisoquinolines, with a brown seaweed-derived alginic acid reported as an effective reusable catalyst. The protocol shows good yields with various aliphatic and aromatic aldehydes, and demonstrates sustainable synthesis of different compounds including a natural spirooxindole. The catalyst was found to be reusable with no significant deterioration in reaction yields observed up to the 6th cycle.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Integrative & Complementary Medicine
Cao Ning, Wang Chang-Hong
Summary: This article reviews the latest research on the biosynthesis of natural compounds TIAs and BCAs, focusing on the role of strictosidine synthase in this process and the sources and substrate specificity of related compounds derived from strictosidine. The presence of six-bladed four-stranded beta-propeller folds in many organisms other than plants may indicate similar functions among different organisms. The expression of the strictosidine synthase gene has a significant impact on the production of various compounds, which are mainly used in plant cell suspension culture for the production of valuable drugs and biosynthesis in other carriers.
CHINESE JOURNAL OF NATURAL MEDICINES
(2021)
Article
Chemistry, Organic
Takanori Shibata, Mio Sasaki, Masafumi Kojima, Mamoru Ito
Summary: The chiral Ir(I)-catalyzed intermolecular reaction of N-carbamoylpyrrole and indole derivatives with alpha,beta-unsaturated carbonyl compounds proceeded with high enantioselectivity, yielding chirally functionalized pyrroles and indoles as formal C-H conjugate adducts. The reaction mechanism was further investigated through deuterium labeling experiments.
Article
Chemistry, Multidisciplinary
Zhen Deng, Liu-Yan Qiu, Wenjie Pan, Baiyu Qian, Jie Chen, Hui Zhang, Qing-Yun Chen, Weiguo Cao, Xiao-Jun Tang
Summary: In this study, the classical Pummerer rearrangement efficiently produced S,O-acetal under specific conditions, and regenerated the reactive intermediate through the co-solvent, enabling the synthesis of 1-thiyl-2,2,2-trifluoroethyl arenes with excellent yields under metal-free conditions.
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Organic
Meng Wang, Ze-Hong Zheng, Mu-Qiu Chen, Gu Zhan, Jie Wang, Qian-Qian Yang, Wei Huang
Summary: A series of tetrahydro-beta-carbolin 1,3-diketone frameworks can be synthesized efficiently under mild conditions using azlactones and indole-2-amides. This reaction exhibits excellent compatibility and can be completed without a metal mediator.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Zhang Xiaoyu, Li Xinyan, Cui Bing, Shao Zhihui, Zhao Mingqin
Summary: In this study, a new Pictet-Spengler oxidation reaction was developed using a pincer manganese catalyst, leading to the synthesis of 12 THBC products. The compounds exhibited good antioxidant activity, indicating their potential application in various fields.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Jukiya Sakamoto, Daiki Hiruma, Mariko Kitajima, Hayato Ishikawa
Summary: In this study, the collective and efficient asymmetric total syntheses of five beta-carboline-type monoterpenoid indole alkaloid glycosides were successfully achieved in fewer than thirteen steps. The beta-carboline motif was efficiently constructed through a Pictet-Spengler reaction with alpha-cyanotryptamine, followed by the removal of the cyano group and autoxidation (aromatization). Furthermore, bioinspired reactions were developed to provide different alkaloid skeletons.
Article
Chemistry, Organic
Qi-Wen Shen, Wei Wen, Qi-Xiang Guo
Summary: The first catalytic asymmetric cascade Heck-alkylation reaction of NH2-unprotected amino acid esters with N-(2-iodophenyl)allenamides is reported in this work. The reaction proceeds smoothly using a combining catalytic system comprising a chiral aldehyde, a chiral palladium complex, and the Lewis acid ZnCl2, giving optically active alpha-alkyl tryptophan derivatives in moderate to good yields and excellent enantioselectivities. The target products can be converted into other structurally complex chiral indoles without the loss of enantioselectivities.
Article
Chemistry, Organic
Takahito Kuribara, Koki Matsumoto, Sho Nagasawa, Yuta Suzuki, Masaya Nakajima, Yasumasa Hamada, Tetsuhiro Nemoto
Article
Chemistry, Organic
Jun Ueda, Shingo Harada, Ayaka Kanda, Hiroki Nakayama, Tetsuhiro Nemoto
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Tsubasa Ito, Shingo Harada, Haruka Homma, Hiroki Takenaka, Shumpei Hirose, Tetsuhiro Nemoto
Summary: This study developed a new method for achieving highly enantioselective dearomatization of chemically inert arenes, leading to the synthesis of polycycles with multiple stereogenic centers. Mechanistic investigations revealed the origin of chemo- and enantioselectivity in the reaction process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Applied
Mai Yanagawa, Shingo Harada, Shumpei Hirose, Tetsuhiro Nemoto
Summary: The study developed a rhodium-catalyzed C-H functionalization reaction for synthesizing 2,3-fused indole variants using an alpha,beta-unsaturated enone as a directing group and electrophile. This annulation enabled the rapid assembly of valuable hydrocarbazolones from readily available indoles, and computational investigations were conducted to elucidate the reaction pathway and site-selectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Jun Ueda, Shingo Harada, Mayu Kobayashi, Mai Yanagawa, Tetsuhiro Nemoto
Summary: A dual catalyst system consisting of maleic acid and Schreiner's thiourea was used to successfully synthesize a spiroindolenine core, providing a new approach for synthetic strategies that were previously difficult to achieve. Computational studies revealed a unique macrocyclic transition state that lowered the activation energy of the spirocyclization reaction.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Tsubasa Ito, Hiroki Takenaka, Haruka Homma, Shingo Harada, Tetsuhiro Nemoto
Summary: An asymmetric intramolecular cyclopropanation reaction under silver catalysis has been developed, producing enantioenriched gamma-lactam fused cyclopropane commonly found in bioactive molecules and pharmaceuticals. The fused cyclopropane was efficiently converted into drug candidate molecules in short steps, highlighting the utility of this method. Computational investigations based on density functional theory clarified the chemoselectivity between the desired cyclopropanation and overoxidation process observed experimentally.
TETRAHEDRON LETTERS
(2021)
Article
Chemistry, Organic
Takahito Kuribara, Masaya Nakajima, Tetsuhiro Nemoto
Summary: The article elucidates the selectivity difference between platinum and palladium in the Friedel-Crafts-type synthesis reaction, and reveals the mechanism of the behavioral differences of the two metals through density functional theory calculations and experimental studies.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Masaya Nakajima, Yusuke Adachi, Tetsuhiro Nemoto
Summary: This study demonstrated the potential of computational simulation-based natural product syntheses as an indispensable resource in the field of organic synthesis. The authors reported the asymmetric total syntheses of several resveratrol dimers based on a comprehensive computational simulation of their biosynthetic pathways.
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
Masaya Nakajima, Yusuke Adachi, Tetsuhiro Nemoto
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Takahito Kuribara, Masaya Nakajima, Tetsuhiro Nemoto
Summary: Ligand design plays a crucial role in enhancing the performance of light-enabled catalytic processes. In this study, the authors synthesized a visible-light-activated secondary phosphine oxide ligand and applied it to Pd-catalyzed radical cross-coupling reactions. Through molecular design aided by computational calculations, the ligand enables ligand-to-Pd(II) and Pd(0)-to-ligand single-electron transfer under visible-light irradiation, facilitating radical cross-coupling reactions.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Dongil Choi, Noa Takahashi, Haruka Maruoka, Shingo Harada, Alina Nastke, Harald Groeger, Tetsuhiro Nemoto
Summary: We developed an enantioselective synthetic method utilizing Ir-catalyzed asymmetric hydrogenation to introduce chirality at the benzylic position, followed by Pd-catalyzed cascade cyclization for tricyclic molecular framework construction and Ag nitrene-mediated C-H amination for tetrasubstituted carbon center creation. This method provides access to a functionalized seven-membered ring-fused indole skeleton with a hydroxymethyl branch in the tetrasubstituted carbon.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Yoshinori Hashimoto, Shingo Harada, Ryosuke Kato, Kotaro Ikeda, Jannis Nonnhoff, Harald Groeger, Tetsuhiro Nemoto
Summary: This study reported a catalytic approach for the formal synthesis of more than 20 types of sarpagine/macroline alkaloids, with two key steps being the amide insertion reaction using cheap copper and biocatalytic asymmetric desymmetrization.
Article
Chemistry, Organic
Takahito Kuribara, Ayahito Kaneki, Yuma Mihara, Honoka Yuba, Tetsuhiro Nemoto
Summary: In this study, we describe a scandium-catalyzed regioselective synthesis of 5-carbonyl-4-hydroxybenzofurans via a phenol-directed intramolecular Friedel-Crafts reaction. This method was successfully applied for the total synthesis of furanoflavones. Experimental and theoretical calculations suggest that hydrogen bond interactions between the phenolic hydroxy group and the scandium complex enable regioselective intramolecular cyclization.
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, Physical
Yu Matsuda, Masaya Nakajima, Tetsuhiro Nemoto
Summary: Transition metal-catalyzed photoreactions have been extensively reported, but the development of ligands for these reactions is limited. This study successfully synthesized acridine-containing PNP-pincer ligands and found that the platinum complex induced photoreactions of olefins under visible light irradiation. These reactions revealed unknown reactivities of transition metals that could not be achieved with existing well-known ligands.
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
