Stereoselective synthesis of 1,1′-linked α-l-lyxopyranosyl β-d-glucopyranoside, the proposed biosynthetic precursor of the FG ring system of avilamycins

The non-reducing disaccharide β-d-Glcp-(1↔1)-α-l-Lyxp1 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-α-l-lyxopyranosyl trichloroacetimidate 13. Reaction of 13 with 2,3,4,6-tetra-O-acetyl-d-glucopyranose gave the disaccharide as mixture of 1β,1′α and 1β,1′β 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 1β,1′α disaccharide as a single isomer in 72% yield. Interestingly, the formation of α-glucosides was not observed in any case, regardless of the use of glucose as glycosyl donor or acceptor.

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