Conversion of Phorbol into Des-D-Ring Tricycle and Crotonianoid B via Peroxidation Reaction

Org Lett. 2024 May 24;26(20):4335-4339. doi: 10.1021/acs.orglett.4c01363. Epub 2024 May 13.

Abstract

Phorbol (1) has a tetracyclic ABCD-ring and is readily isolable from a natural source. We previously synthesized 1 and 16 structurally related natural products using common ABC-ring intermediate 2. Here we report a new synthetic route to 2 using 1 as a starting material. Key features of the synthesis are chemoselective removal of the D-ring via cyclopropane opening, peroxidation, and retro-aldol reactions. The high utility of the peroxidation was further demonstrated in the first synthesis of crotonianoid B (9).