Synthesis of diazomethyl beta-D-galactopyranosyl and beta-D-glucopyranosyl ketones. Potential affinity-labeling reagents for carbohydrate-binding proteins.

3,7-Anhydro-1-deoxy-1-diazo-D-glycero-L-manno-2-octulose (6a; diazomethyl beta-D-galactopyranosyl ketone) and 3,7-anhydro-1-deoxy-1-diazo-D-glycero-D-gulo-2-octulose (6b; diazomethyl beta-D-glucopyranosyl ketone) have been prepared. Readily available C-glycosyl compounds possessing the appropriate stereo-chemistry and hydroxyl-group protection, viz., per-O-acetyl-2,6-anhydroheptononitriles and per-O-acetyl-2,6-anhydroheptonamides, were employed as precursors to per-O-acetyl-2,6-anhydroheptonic acids. These key intermediates were then converted into mixed carboxylic-carbonic acid anhydrides, and these caused to react with diazomethane, to give the corresponding per-O-acetyl-3,7-anhydro-1-deoxy-1-diazo-2-octuloses. Zemplén deacetylation gave, stereospecifically, the crystalline target-molecules in good overall yield. It is proposed that such C-glycosyl compounds as 6a and 6b, which possess the diazoacetyl functional groups as their "aglycon", will be useful as enzyme-activated irreversible inhibitors (suicide substrates) of glycosidases, and as photoaffinity-labeling reagents and classical affinity-labeling reagents for carbohydrate-binding proteins.