Synthetic approach toward the indole alkaloid TMC-205, 6,7-secoagroclavine, aurantioclavine, clavicipitic acid, and caulindoles A–D

Abstract

Herein, we report a concise and efficient one-pot total synthesis of TMC-205 in 77% overall yield (gram-scale) using only two simple and streamlined steps. In the proposed approach, a novel Heck-dehydration reaction and a practical aromatic carboxylic acid introduction strategy are reported, which are characterized by high atom economy, excellent regioselectivity and stereoselectivity (E-isomer). This synthesis protocol is protecting group-free, redox neutral, environmentally benign, and features simple operation steps. Through the implementation of this new, efficient and scalable synthesis method, the formal synthesis of a series of novel meroterpenoid natural products can be successfully realized. Moreover, the synthetic strategy and methodologies demonstrated in this paper are useful and can be easily extended to the preparation of other related biologically active molecules.