Stereoselective Synthesis of (-)-Verazine and Congeners via a Cascade Ring-Switching Process of Furostan-26-acid.

An efficient synthetic strategy for three natural seco-type cholestane alkaloids isolated from the Veratrum plants, based on commercially available naturally occurring and abundant (−)-diosgenin (1), as exemplified in the concise asymmetric synthesis of (−)-verazine (4), (−)-veramiline (5) (proposed structure), and its 22-epimer, (−)-oblonginine (6), is presented. This work highlights the application of a cascade ring-switching process of (−)-diosgenin to achieve the E-ring opening and construction of chiral six-membered lactone challenges in seco-type cholestane alkaloid synthesis. This approach enables the synthesis of related natural and nature-like novel cholestane alkaloids, opening up opportunities for more extensive exploration of cholestane alkaloid biology.