Efficient synthesis of the functional central core lactides, a constituent of antibiotic fattiviracins

Abstract

An efficient convergent synthetic method has been developed for preparation of various stereoisomers and derivatives of fattiviracins via a common lactide. The synthetic route comprises seco acids prepared by the β-selective glycosylation of chiral 3-hydroxy-4-pentanoate obtained by enzymatic kinetic resolution. The regioselective protection of four individual hydroxy groups was achieved via the 4,6- O-benzylidenation of the glucose moiety from its TMS ethers. The dimeric cyclization of the seco acids under control of reaction concentration afforded the desired lactide without using KH. Our convergent synthetic method was successfully applied to direct installation of side chains to the lactide by cross metathesis to synthesize fattiviracin derivatives. We achieved improvements to the reported method with respect to: (1) synthesis of a convergent synthetic intermediate; (2) stereoselectivity in glycosylation; and (3) establishment of a low cost route suitable for large scale synthesis.