Chemoenzymatic Synthesis of α-(1→3)-Gal(NAc)-Terminating Glycosides of Complex Tertiary Sugar Alcohols

The scope of glycosyltransferases in the synthesis of oligosaccharide analogues has been expanded to include the use of “retaining” enzymes acting on complex tertiary C -branched disaccharide acceptors. The enzymes studied were α1,3-galactosyltransferase (α1,3-GalT, EC 2.4.1.151), which uses Galβ1→4Glcβ-OR as the acceptor, and recombinant blood group A [α1,3-GalNAc transferase (GTA), EC 2.4.1.40] and B [α1,3-Gal transferase (GTB), EC 2.4.1.37] glycosyltransferases, which use Fucα1→2Galβ-OR as the acceptor in their biosynthetic reactions. Chemical synthesis produced acceptor analogues in which the ring carbon bearing the OH groups undergoing enzymatic glycosylation in the natural reactions had their C−H bond replaced with a C -methyl or C -propyl bond. The tertiary C -methyl alcohols proved to be kinetically competent substrates which permitted the enzymatic preparation of the expected product trisaccharides in near quantitative yields.