Synthesis of the lipoteichoic acid of the streptococcus species DSM 8747

Abstract

The lipoteichoic acid (LTA) of the Streptococcus species DSM 8747 consists of a Beta-D-galactofuranosyl diacylglycerol moiety (with different acyl groups) that is linked via 6-0 to a poly(glycerophosphate) backbone; about 30% of the glycerophosphate moieties carry at 2-0 hydrolytically labile o-alanyl residues. As typical LTA for this array of compounds LTA la was synthesized. To this end, from o-galactose the required galactofuranosyl building block 5 was obtained. The anomeric stereocontrol in the glycosylation step with 1,2-0-cyclohexylidene-sn-glycerol (4) was based on anchimeric assistance, thus finally leading to the unprotected core glycolipid 16. Regioselective protection and de protection procedures permitted the defined attachment of the pentameric glycerophosphate 3 to the 6-hydroxy group of the galactose residue. Introduction of four D-alanyl residues led after global deprotection and purification to target molecule la possessing on average about two D-alanyl residues at 2-0 of the pentameric glycerophosphate backbone, thus being in close accordance with the structure of the natural material.