Total Synthesis of Aplysiasecosterols A and B, Two Marine 9,11-Secosteroids

Abstract

The total synthesis of aplysiasecosterols A and B has been accomplished. Key features of the synthesis include the Suzuki−Miyaura coupling of each AB-ring segment and common D-ring segment. The AB-ring segment of aplysiasecosterol B was synthesized by Shi asymmetric epoxidation as a key reaction. The common D-ring segment was constructed by stereoselective hydrogenation and Sharpless asymmetric dihydroxylation as key reactions. This late-stage convergent synthesis, which has rarely been reported in secosteroid synthesis, can be adapted to many 9,11-secosteroids.

Controllable skeletal reorganizations in natural product synthesis

“…75,76 Aplysiasecosterol A, which shares its core skeleton with the pinnigorgiols, was convergently synthesized by the Li group 77 and the Kigoshi group. 78 In 2021, the Gui group reported the first synthesis of pinnigorgiols, which they accomplished by means of a bioinspired skeletal reorganization for converting the classical steroid skeleton to the complex cage skeleton. 79 In 2016, the Kigoshi group proposed that the structurally similar natural product aplysiasecosterol A ( 48 ) might be derived from aplysiasecosterol B ( 45 ) through an α-ketol rearrangement, followed by a vinylogous α-ketol rearrangement and hemiketal formation (Scheme 7A).…”