Neighboring group participation in epoxide ring cleavage in reactions of some 16α,17α-oxidosteroids with lithium hydroperoxide

In order to work out a new approach to the synthesis of the potent anti-tumor saponin OSW-1 aglycone, 16α,17α-oxidosteroids were treated with acids, bases and lithium hydroperoxide. Acids caused Wagner–Meerwein type rearrangements irrespective of the side-chain structure. 16α,17α-Epoxides proved resistant to bases unless a 22-carbonyl group was present; in the case of 22-esters or 22-ketones the epoxide rings were cleaved with base and the corresponding allylic alcohols were formed. The epoxide ring cleavage of 16α,17α-oxido-22-ester with lithium hydroperoxide was followed by lactonization of the intermediate 16β,17α-dihydroxy acid. The saponin OSW-1 aglycone was obtained by reaction of the lactone with isoamyllithium.