New syntheses of naturally occurring cytotoxic plant steroids (E)‐ and (Z)‐volkendousin (1 and 2) and their acetonides 1a − a potent selective cell growth inhibitor − and 2a have been accomplished, starting from diosgenin (overall yields of 1.2%, 0.7%, 1.9%, and 1.1% for 1, 2, 1a, and 2a, respectively), and also from 16‐dehydropregnenolone (overall yields of 9.4%, 2.5%, 14.0%, and 3.8% for 1, 2, 1a, and 2a, respectively). The efficiency of the stereospecific Petrow rearrangement and the straightforward introduction of the α,β‐unsaturated ketone functionality, by a Wharton reaction, illustrate the utility of this new synthetic strategy.