Article
Chemistry, Organic
Shiyuan Kang, Yinxia Wu, Min Hu, Ying Ma, Xiangdi Huang, Zhen Hao, Xiujuan Li, Wen Chen, Hongbin Zhang
Summary: The asymmetric total synthesis of vinorine, a complex cage-like alkaloid, has been achieved using a flexible approach. Key steps in this synthesis involve a rearrangement/cyclization reaction to form the functional 9-azabicyclo[3.3.1]nonane scaffold, a high yield indole annulation to create a common intermediate for sarpagine-ajamaline type alkaloids, and a rearrangement reaction to construct the C15-C20 bond.
Article
Chemistry, Organic
Matteo Faltracco, Said Ortega-Rosales, Elwin Janssen, Razvan C. Cioc, Christophe M. L. Vande Velde, Eelco Ruijter
Summary: The unexpected discovery in a seemingly trivial reaction led to the selective formation of a new carbazole product. This reaction, by carefully varying substituents, revealed a complex cascade mechanism with at least 10 elementary steps that could be directed towards different carbazole derivatives.
Article
Chemistry, Multidisciplinary
Wai Fung Cheng, Shiqiang Ma, Yin Tung Lai, Yuen Tsz Cheung, Kornkamon Akkarasereenon, Yiqin Zhou, Rongbiao Tong
Summary: An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed using bismuth tribromide as both an efficient Lewis acid and a bromide nucleophile source. This approach enables the construction of highly functionalized 9-azabicyclo[3.3.1]nonanes, which are valuable building blocks for alkaloid natural products and drug molecules. The application of this method to the total synthesis of six indole alkaloids demonstrates its significant synthetic utility.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Yingfu Lin, Rui Zhang, Di Wang, Tim Cernak
Summary: Efficient chemical synthesis is crucial for meeting the future demands of pharmaceuticals, materials, and agrochemicals. While the automation of retrosynthetic analysis for moderately complex molecules has been ongoing for decades, the vast number of possible routes has posed challenges for computer hardware and software until recently. In this study, we introduce a computational strategy that combines computer-aided synthesis planning with molecular graph editing to minimize the synthetic steps needed for producing alkaloids. Through the utilization of high-impact key steps identified in computer-generated retrosynthesis plans using graph edit distances, we have successfully achieved an enantioselective three-step synthesis of (-)-stemoamide.
Article
Chemistry, Multidisciplinary
Remi Andres, Qian Wang, Jieping Zhu
Summary: A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been achieved by several key steps, including a catalyst-controlled asymmetric Pictet-Spengler reaction, oxidative cleavage, and intramolecular nucleophilic addition. The synthesis confirmed the absolute configuration of these natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Guang Li, Nicolas Gaeng, Cyril Piemontesi, Qian Wang, Jieping Zhu
Summary: The enantioselective total synthesis of three monoterpene indole alkaloids was successfully achieved by introducing chirality, using MOM ether as a protective group, and employing a domino reaction to construct the indole and piperidine rings. The synthesis confirmed the absolute configuration of these natural products according to the biogenetic hypothesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Audrey Mauger, Maxime Jarret, Aurelien Tap, Remi Perrin, Regis Guillot, Cyrille Kouklovsky, Vincent Gandon, Guillaume Vincent
Summary: We synthesized highly strained pentacyclic caged framework of mavacuran alkaloids and successfully achieved the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. A strategy involving late-stage Michael addition and intermolecular 1,4-addition reactions was designed. The first total syntheses of C-profluorocurine and C-fluorocurine were achieved through dihydroxylation of C-mavacurine and a pinacol rearrangement, respectively.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Organic
Stefan van Rootselaar, Evert Peterse, Daniel Blanco-Ania, Floris P. J. T. Rutjes
Summary: Piperidine alkaloids are a type of alkaloid characterized by a six-membered nitrogen-containing heterocycle. They are mainly found in plants and have interesting biological and pharmacological activities. The synthesis of piperidine alkaloids and their derivatives is important for drug discovery due to their low natural abundance.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sandra Hernandez-Ibanez, Ana Sirvent, Miguel Yus, Francisco Foubelo
Summary: The stereocontrolled synthesis of 1-substituted homotropanones was achieved using chiral N-tert-butanesulfinyl imines as intermediates. Key steps in this methodology include the reaction of organolithium and Grignard reagents with hydroxy Weinreb amides, chemoselective N-tert-butanesulfinyl aldimine formation from keto aldehydes, decarboxylative Mannich reaction with beta-keto acids of these aldimines, and organocatalyzed L-proline intramolecular Mannich cyclization. The utility of the method was demonstrated with the synthesis of (-)-adaline and its enantiomer (+)-adaline.
Article
Chemistry, Multidisciplinary
Yun-Peng Zou, Zheng-Lin Lai, Meng-Wei Zhang, Jianzhao Peng, Shuai Ning, Chuang-Chuang Li
Summary: The first total synthesis of (+/-)- and (-)-daphnilloninB, a daphnicyclidin-type alkaloid with a novel hexa-cyclic core, was achieved through a series of chemical reactions. The B/C/D ring system was efficiently constructed using a mild intramolecular cycloaddition and a GrubbsII catalyst-catalyzed radical cyclization. The E/F fused ring system was synthesized via a diastereo-selective intramolecular Pauson-Khand reaction. The challenging hexa-cyclic core was reassembled from a hexa-cyclic framework found in calyciphylline A-type Daphniphyllum alkaloids through a unique Wagner-Meerwein rearrangement.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Wei Xu, Taimin Wang, Xin Zhou, Lijing Fang, Chen Zhang, Hongbin Zhai, Bin Cheng
Summary: A concise total synthesis of (+/-)-pileamartines A and B, alkaloids with an unprecedented tetracyclic skeleton, was achieved. Key steps including NHC-catalyzed tandem reaction, diastereoselective reductive allylation, and RCM were used to establish the core structure.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Yulong Zhao, Jiaxin Li, Ruize Ma, Feifei He, Hongliang Shi, Xiaoguang Duan, Huilin Li, Xingang Xie, Xuegong She
Summary: The total synthesis of the indole alkaloid (-)-an-dranginine has been achieved in 10 steps, involving key reactions including nucleophilic addition of acetylenyl anion, intramolecular N-alkylation reaction, and dienyne metathesis cascade reaction.
Article
Chemistry, Organic
Ali Mansour, Fabien Gagosz
Summary: Two concise and complementary routes to the polycyclic alkaloid (+/-)-brevianamide A from readily available amino acid building blocks are presented. The key to the synthesis is the strategic use of a gold(I)-catalyzed cascade process, which quickly assembles the characteristic pseudoindoxyl motif of the natural product and the two adjacent quaternary centers in a single step. This sequence exemplifies the structural complexity achievable with gold catalysis and allows for the shortest and highest-yield synthesis of (+/-)-brevianamide A to date.
Article
Plant Sciences
Elisa Bonandi, Francesca Foschi, Cristina Marucci, Giuseppe Paladino, Marcello Luzzani, Daniele Passarella
Summary: This review summarizes the main strategies for the total synthesis of vincamine and congeners, and presents a semi-synthesis method of (+)-vincamine using tabersonine as the starting material. Characterization and quantification of main impurities are discussed, along with reporting HPLC conditions, structural elucidation, and NMR data for four of them.
PHYTOCHEMISTRY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Atsushi Nakayama, Tenta Nakamura, Toshihiro Zaima, Saho Fujimoto, Sangita Karanjit, Kosuke Namba
Summary: The concise total synthesis of tronocarpine, a chippiine-type indole alkaloid, was achieved through a one-pot construction of a pentacyclic skeleton. This strategy, controlled by the stereocenter at the C14 position, can be used to synthesize other chippiine-type alkaloids with azabicyclo[3.3.1]nonane skeletons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
