Bufadienolides. 21. Synthesis of Cinobufagin from Bufotalin

A synthetic method was developed for transformation of bufotalin (la) to cinobufagin (5b). The procedure was based on dehydration of bufotalin acetate (1b) to olefin 2 which upon treatment with hypobromous or hypoiodous acid afforded halohydrin 4. Treatment of halohydrin 4 with either activated alumina or pyridine yielded cinobufagin acetate (5a). Selective acid-catalyzed hydrolysis of diacetate 5a was employed to obtain cinobufagin (5b). A number of other cinobufagin derivatives were prepared including deacetylcinobufagin (5d) and the new bufadienolide 3-epicinobufagin (9a).