Stereocontrolled synthesis of withanolide D and related compounds

Abstract

The synthesis of withanolide D, a withanolide having a hydroxy group at the C-20 position, has been accomplished from pregnenolone. The key reactions are based on successful stereochemical control at the C-22 position involving γ-coupling reaction of a lithium enolate with a protected 20-hydroxy-22-aldehyde, and allyl sulphoxide–sulphenate rearrangement of 2,4-dien-1 -one 6β-sulphoxide to introduce the 4β-hydroxy-2,5-dien-1-one system. The related natural withanolides, physalolactone B, deacetyl-physalolactone B, and 3α,20R-dihydroxy-1-oxowitha-5,24-dienolide were also synthesized via a common intermediate for withanolide D.