A Modular Enantioselective Approach to Construction of the Macrolactone Core of Polycavernoside A

A program directed toward a total synthesis of polycavernoside A is described. The synthesis of five building blocks is detailed. The first of two electrophilic units, the lactone 3, was prepared in four steps from the known enantiomerically pure oxirane 15. Pyranyl aldehyde 5 was elaborated in turn from L-malic acid via 10. While the route to 30 involved 3 as a starting material, dithiane 2 was obtained in a straightforward manner from 10 as well. The merging of the chiral sectors could not be accomplished by way of the lithiated dithianyl anions, presumably as a consequence of their heightened basicity. The strategic incorporation of the trienyl sector was accomplished, although no attempt was made to control the diastereoselectivity of the process.