Synthetic modifications of withanolides with an α-orientated side-chain

Abstract

In view of the antitumour activity of withanolide E [(20S,22R)-5β,6β-epoxy-14α,17β, 20-trihydroxy 1-oxowitha-2,24-dienolide] and 4β-hydroxywithanolide E, synthetically modified analogues were prepared. In these compounds, the α-orientation of the side-chain was retained. Its degree of bending with respect to the carbocyclic skeleton depends on the presence or absence of the 14α-OH group. Elimination of this group leads to the formation of the 14,20-oxido-bridged and Δ¹⁴-compounds. Epoxidation of the latter afforded 14α,15α-epoxides. With the exception of several 5,6-chlorohydrins, most compounds possess an epoxide ring, allylic or homoallylic with respect to the ring A enone.