(+)-Zaragozic acid C: Synthesis and related studies

Article abstract of DOI:10.1021/ja00136a008

The asymmetric synthesis of the potent squalene synthase inhibitor (+)-zaragozic acid C is described. The synthesis allows for the preparation of multigram quantities of the dioxabicyclooctane core common to all members of this class of fungal metabolites. Supporting studies include (1) the use of [Cr(OAc)₂·H₂O]₂ for the stereoselective reduction of ynones to trans enones, (2) an investigation of the diastereoselective dihydroxylation of γ-alkoxy-α,β-trans enones, and (3) nucleophilic addition of Me₃SiC≡CLi to a dioxabicyclooctanone, wherein the product diastereoselectivity is observed to vary as a function of cosolvents (tertiary amines) and additives (LiBr). In addition, an acylation protocol is reported which permits the regioselective installation of the C(6) O-acyl side chain.