Structural Modification of Mevinolin

Article abstract of DOI:10.1021/jo00145a029

Synthetic strategies are described for modifying the side-chain ester and lactone moieties of mevinolin (1), a potent, competitive HMG-CoA reductase inhibitor isolated from cultures of Aspergillus terreus.A general route for preparing side-chain ether analogues of 1 is disclosed.Central to the success of this multistep route is the use of a method for reversibly masking the lactone moiety as a hemiacetal ether.The merit of this strategy is demonstrated again in the route developed for elaborating mevalonate analogue 11 from 1.Finally, a new, versatile, and efficientmethod is presented for homologating five- and six-membered lactones and is used to prepare carboxylate 27, a homologue of 1.