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

Abstract

In view of the antitumour activity of withanolide E [ (20S,22R) -5P,6~-epoxy-l4a,l7P,20-tri hydroxy- 1 -oxowitha-2,24-dienolide] and 4p- hydroxywithanolide E, synthetically modified analogues were prepared. In these compounds, the a-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 14a- OH group. Elimination of this group leads to the formation of the 14,20-oxido-bridged and A14- compounds. Epoxidation of the latter afforded 14a,15a-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