Total Synthesis of Indotertine A and Drimentines A, F, and G

摘要

The pyrroloindoline alkaloids attract wide interest from the fields of chemistry, biosynthesis, and biology. From a structural perspective, they can be divided into several classes that vary in the substituent on C3a of the pyrroloindoline core, including heteroatoms, arenes, aliphatic groups, and another pyrroloindoline motif. Accordingly, a series of strategies have been developed for the synthesis of the above pyrroloindoline classes. Notably, a structurally complex aliphatic side chain linked to the C3a position is rather rare. The drimentine alkaloids (1-4, Scheme 1), which exhibit anticancer, antibacterial, antifungal, and anthelmintic properties, possess the latter substitution mode. A stereocontrolled method to form the C10b-C12 bond of the drimentine scaffold is highly desired for the synthesis of these compounds. Indotertine A (5, Scheme 1) with an unprecedented, but biosynthetically relevant, skeleton was recently discovered.The biosyn-thetic relationship between 3 and 5 is postulated in Scheme 1. Acidic activation of the germinal diamine moiety of 3 may generate an iminium species 6, which could undergo an irninium-olefin cyclization followed by a proton elimination of the cationic intermediate 7. Herein, we report the first total synthesis of drimentines A, G, and F (1-3), exploiting a photocatalyzed radical conjugate addition to address the problem of the C10b-C12 bond formation; a synthesis of indotertine A (5), guided by the above biosynthetic hypothesis, is also described.