A novel approach in drug discovery: Synthesis of estrone-talaromycin natural product hybrids

Hetero-Diels - Alder reaction of the steroidal exocyclic enol ethers 14 and 15, obtained from the secoestrones 8 and 9 by reduction, iodoetherificatio n, and elimination, with ethyl O-benzoyldiformylacetate (16) leads to the s piroacetals 17 and 18 as a mixture of four diastereomers. Reduction of the major diastereomers 17a and 18 a with DIBAH and subsequent hydrogenation yi elds the novel natural product hybrids 21, 23, 24, and 25, which possess th e structural features of the steroid estrone (7) and the mycotoxin talaromy cin 6.