Synthesis of the Epimeric Secosteroids Strophasterols A and B

Abstract

Tw oe pimeric rearranged ergostanes,s trophasterols Aa nd B, with an unprecedented carbon skeleton were synthesized from ergosterol, both in 17 steps via ac ommon secosteroidal intermediate.T he conversion of ergosterol into the pivotal intermediate involved an efficient acid-catalyzed double-bond migration from ring Bt or ing D, oxidative cleavage of the double bond, and acompletely diastereoselective acyl radical cyclization to form an isolated cyclopentanone ring unique to this recently discovered family of steroidal compounds produced by mushrooms.T he intermediate was transformed stereodivergently into two epimeric cyclopentane derivatives through hydrogenation using two types of catalysts. One epimer was elaborated into strophasterol Bb yu tilizing peracid oxidation of an iodide to providea ne poxide directly, and the other epimer was elaborated into strophasterol A, which is knownt ob eas uppressor of endoplasmic reticulum stress.