Bufadienoiides. 14. Synthesis of Bufotalien, 15a-Hydroxybufalin, and Resibufogenin

Conversion of 14-dehydrobufalin (2a) to bufotalien (4a) was accomplished. Peracid Oxidation of 3β-acetoxy-14-dehydrobufalin (2b) was employed to obtain 14α,15α-epoxide 5b. Sulfuric acid catalyzed opening of epoxide 5b was used to complete a route to 15α-hydroxybufaiin (6b). Treatment of diol 6b with methanesulfonyl chloride led to a new synthesis of 3β-acetoxyresibufogenin (3b). Conversion of 14-dehydrobufalin to the halo-hydrins represented by structures 6d-g followed by treatment with basic alumina or hot pyridine afforded resibufogenin in good yield. The epoxide formation catalyzed by alumina was also shown to yield 14α-artebufogenin (8b).