Stereoselective synthesis of 1,10-linked a-L-lyxopyranosyl b-D-glucopyranoside, the proposed biosynthetic precursor of the FG ring system of avilamycins

Abstract

The non-reducing disaccharide b-D-Glcp-(1M1)-a-L-Lyxp 1 had been proposed to be an early intermediate during the biosynthesis of avilamycin A [Boll, R.; Hofmann, C.; Heitmann, B.; Hauser, G.; Glaser, S.; Koslowski, T.; Friedrich, T.; Bechthold, A. J. Biol. Chem. 2006, 281, 14756 14763]. This work describes a comparison of two strategies for the synthesis of 1 and its 2-amino-2- deoxy analog with either the glucose or the lyxose moiety acting as the glycosyl donor. The best results in terms of stereoselectivity and yield were obtained with 2,3,4-tri-O-acetyl-a-L-lyxopyranosyl trichloroacetimidate 13. Reaction of 13 with 2,3,4,6-tetra-O-acetyl-Dglucopyranose gave the disaccharide as mixture of 1b,10a and 1b,10b isomers in a ratio of 10:1 and a yield of 50%. Reaction of 13 and 3,4,6-tri-O-acetyl-2-azido-2-deoxy-D-glucopyranose yielded the desired 1b,10a disaccharide as a single isomer in 72% yield. Interestingly, the formation of a-glucosides was not observed in any case, regardless of the use of glucose as glycosyl donor or acceptor.