Stereoselective syntheses of dihydroxerulin and xerulinic acid, anti-hypocholesterolemic dyes from the fungus Xerula melanotricha

The title compounds 2 and 3, which are inhibitors of the biosynthesis of cholesterol, were synthesized in a convergent and perfectly stereoselective manner. In the key step, bromobutenolide 6 (obtained from levulinic acid in two steps) was coupled with either of the novel bis(stannanes) trans,cis, -trans-35 or trans,trans,trans-35 [each accessible from 3-(tributylstannyl)allyl alcohol (17) in four steps], giving gamma-al-kylidenebutenolide trans,trans,trans-32. This compound was coupled with iododiyne 42 or the bromoenediynoate 44 leading to dihydroxerulin (2) and to the (trimethylsilylethyl) ester 45 of xerulinic acid, respectively. Deprotection of the latter provided totally synthetic xerulinic acid (3) for the first time.