Steroids and related natural products. Part XCI. Synthesis of the cardenolides canarigenin and uzarigenin

Abstract

From 3β,14-dihydroxy-5β,14β-card-20(22)-enolide (digitoxigenin)(III), new formal total syntheses of canarigenin [3β,14-dihydroxy-14β-carda-4,20(22)-dienolide](IIa) and uzarigenin [3β,14-dihydroxy-5α,14β-card-20(22)-enolide](Ic) have been completed. The route found most convenient involved direct oxidation of digitoxigenin (III) with t-butyl hypochlorite to yield the 4β-chloro-3-ketone (IVb). Dehydrohalogenation to the 4-en-3-one (canarigenone)(V) was followed by selective reduction with lithium hydrido-tri-t-butoxyaluminate to afford canarigenin (IIa) and with lithium borohydride to yield uzarigenin (Ic).