Steroids and Related Natural Products. 94. Synthesis of Toad Venom Cardenolides

Some species of the milkweed butterfly family (Danaidae) have been found by Reichstein and colleagues to contain cardenolides. The occurrence of such cardiac active plant constituents in these particular butterflies has been nicely correlated with their feeding habits which involve certain cardenolide containing plants (e.g., from the Asclepiadaceae family) and their need for an exogenous source of defensive substances. In 1970, Meyer and colleagues reported the presence of seven cardenolides in the Chinese toad venom preparation Ch'an Su. The constituents included digitoxi-genin (la), sarmentogenin (lb), periplogenin (2a), and two previously unknown 14, 15 β-epoxycardenolides (3a and 3b). Whether such cardenolides represent a normal biosynthetic pathway in venom production characteristic of certain am-phibians of the Bufonidae family or instead are initially obtained by ingestion of Asclepiadaceae-type plant eating insects poses an interesting biochemical question. However, the discovery4a of two cardenolides bearing suberic acid ester groups (e.g., lc) in Ch'an Su and the more recent isolation of sarmentogenin (lb), 3-suberoylarginine, and 3-pimelo-ylarginine esters from the skin of Bufo vulgaris formosus.