Two approaches to 14,15-secoergostane intermediates for the synthesis of strophasterols

Abstract

Two protected 14,15-secoergostane derivatives suitable as pivotal intermediates for the synthesis of strophasterols A and B, anti-MRSA and neuronal cell-protecting natural products bearing a recently discovered strophastane skeleton, have been synthesized by two different routes. The first approach employed an oxidative cleavage of an α-hydroxy ketone intermediate with the Jones reagent as the key step to reach the targeted secoergostane from ergosterol in ten steps. In the second approach, an unprecedented reaction cascade composed of four reactions enabled us to obtain the secoergostane more efficiently in six steps.

Synthesis of Strophasterols C, E, and F

“…The totally unprecedented steroidal skeleton unique to strophastanes as well as their potential as new drug leads prompted synthetic efforts toward this family of natural products, which recently culminated in the first synthesis of 1 by the Heretsch group and our stereodivergent synthesis of 1 and 2 . − Synthetic studies of 3–7 , each of which has an additional oxygen functionality at the C23 position on the side chain, however, have never been reported. In this communication, we describe the first synthesis of strophasterols C, E, and F ( 3 , 5 , and 6 , respectively), which also enabled the stereochemical confirmation of 3 .…”