Convergent, Enantiospecific Total Synthesis of the Hypocholesterolemic Agent (+)-Compactin

Article abstract of DOI:10.1021/ja00279a041

A convergent, enantiospecific total synthesis of (+)-compactin (1) is described.The strategy for the construction of the (+)-1 centers around a Diels-Alder reaction between chiral dienophile 23 and chiral diene 62 which provides in a single operation access to allylic sulfide 85 possessing the desired configuration at C(8'), C(8a'), and C(1').Dienophile 23 is made readily available by resolution of the known racemic β-nitro acid 66.The synthesis of diene 62 commences with the known epoxide 7 derived from tri-O-acetyl-D-glucal.Diels-Alder adduct 85 is transformed into allylic alcohol 87 which sets the stage for incorporation of the C(2') methyl group.Elaboration of the hexalol portion of compactin with liberation of the C(8') hydroxyl group is achieved via a Grob-like fragmentation on alcohol 95.Acylation 94, subsequent adjustment of the oxidation state at C(1), and demethylation give way to (+)-compactin.