Unified Access to Rearranged Steroids via Controlled B-Ring Remodeling of Ergosterol

Rearranged steroids featuring contracted or modified B-ring architectures, such as the unprecedented 6/5/6/5-fused tetrahydrofuran framework in calvatianone, represent challenging targets within the rigid steroidal scaffold. Herein, we describe a unified synthetic strategy enabling efficient access to calvatianone (1) and herbarulide (2), as well as the first synthesis of (22E,24R)-3β,5α-dihydroxy-ergosta-7,22-dien-6,5-olide (3) and its C5-epimer from readily available ergosterol. The key feature of this approach is a nonradical C5-C6 oxidative cleavage enabled by protecting-group modulation, providing a common rearranged intermediate for downstream diversification. Notably, late-stage formation of the contracted tetrahydrofuran B ring in calvatianone is achieved via a stereoselective intramolecular oxa-Michael cyclization. This strategy also offers new insights into the biosynthetic pathway of these rearranged steroids.