Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/10/2004
Publication Date: 6/10/2004
Citation: Xu, L., Kennedy, S.D., Momany, F.A., Price, N.P. 2004. Application of chirally-deuterated (S)-D-(6-**2H1)glucose to biosynthetic studies of microbial carbohydrates [abstract]. FASEB Summer Research Conference: Microbial polysaccharides of medical, agricultural, and industrial importance, June 5-10, 2004, Tucson, Arizona. p. 12.
Technical Abstract: Deuterated sugars are widely used to elucidate mechanisms of biosynthesis and of chemical reactions, and to confirm assignments of complex NMR or mass spectra. To date, however, there are few reported syntheses for regio- and stereospecifically deuterated pyranoses. Chirally-deuterated (S)-D-(6-**2H1)glucose has been prepared from D-(6,6'-**2H2)glucose by a short step synthesis utilizing (R)-(+)-Alpine-Borane. The key stereoselective reduction step was achieved in 90% yield. This chirally-deuterated monosaccharide has been used to study the biosynthesis and conformation of tunicamine, an 11-carbon dialdose sugar that assumes a quasi-D-ribofuranosyl and pseudo-D-galactopyranosylamine conformation that mimics the transition state of the UDP-N-acetyl-D-hexosamine: polyprenol-P N-acetylhexosamine-1-P family of translocase enzymes. Selectively-labeled tunicamycins produced by Streptomyces chartreusis cultured on chirally-deuterated (S)-D-(6-**2H1)glucose as a sole carbon source were examined, and HSQC and COSY data and constrained NOE parameters have been used to model the translocase transition state. Particularly considered are (i) the spatial relationship of the uracil ring to the quasi-ribosyl moiety; (ii) configuration about the tunicaminyl C5'-C6' bond that determines the spatial arrangement of the quasi-furanose and quasi-pyranose rings; (iii) conformation and anomericity of the 1,1'-glycosidic bonds; and (iv) the spatial arrangement of the N-linked acyl chain with respect to the carbohydrate moiety.