Synthetic Studies on Furanosteroids: Construction of the Viridin Core Structure <i>via</i> Diels–Alder/<i>retro-</i>Diels–Alder and Vinylogous Mukaiyama Aldol-Type Reaction

The synthesis of the viridin class of furanosteroids core skeleton from the readily available 2,3-dihydro-4-hydroxyinden-1-one (6) is described. Our strategy was broken down into three parts: (1) Synthesis of functionalized alkyne oxazoles of type 5; (2) intramolecular Diels–Alder/retro-Diels–Alder reaction of 5 followed by tautomerization and elaboration of R to give silylated furanonaphthols 4 bearing an aldehyde side chain; and (3) annulation of ring A by intramolecular vinylogous Mukaiyama aldol-type cyclization. Two major challenges were faced in the last step: (i) furanonaphthol derivatives bearing a β-hydroxyaldehyde functionality (R1 = OH) suffered from dehydration to the E-enal, which is geometrically incapable of cyclization, and (ii) the functionality at C17 had a strong influence on the conversion of 4 to 3, as exemplified by the failure of the free ketone (X = O) or its derivatives (X = H, OH; X = H, OAc) to cyclize. In the end, success was realized with the analogous C17-norketone (X = H, H).