Regioselective Debenzylation of C-Glycosylpropene

Analogues of cell surface-associated carbohydrates or inhibitors of carbohydrateprocessing enzymes are of great pharmaceutical interest. Therefore, many synthetic efforts have been devoted to mimetics of this class of molecules, such as C-glycosyl compounds, which mimic glycosides by replacement of their exocyclic acetalic oxygen with a methylene group. The C-C linkage provides hydrolytic stability without greatly affecting the carbohydrate structure. The C-glycosyl scaffolds should be suitably functionalized in order to mimic their natural counterpart. Toward this aim, regioselective deprotection can be useful for the introduction of the required functional groups. Here, we present an easy procedure for the regioselective deprotection of 3-C-(2, 3, 4, 6-tetra-O-benzyl-α-d-glucopyranosyl)prop-1-ene (1)1 at glycon position 2 and of 3-C-(1, 3, 4, 6-tetra-O-benzyl-α-d-fructofuranosyl)prop-1-ene (4)2 at glycon position 1, respectively. Reaction of the fully benzylated C-glycosylpropene with molecular iodine affords a cyclic iodoether (2 or 5), which upon reductive elimination restores the double bond and a free hydroxyl group. The overall process results in regioselective debenzylation, giving products 3 and 6, respectively. The iodocyclization reaction first involves formation of the iodonium ion, on which the oxygen of the neighboring benzyl ether can act as a nucleophile in a 5-exotype cyclization, with subsequent loss of the benzyl group as benzyl iodide, in an intramolecular process (Scheme 17.1). This regioselective deprotection has been successfully used for the synthesis of a variety of biologically relevant carbohydrate mimetics, such as C-glycosyl derivatives of glucosamine and mannosamine, 3 mimics of α-and β-N-acetyllactosamine, 4 N-acetylgalactosamine, 5 C-glycosyl nojirimycins, 6-8 sugar azido acids, 9 fructose-derived scaffolds, 10 and rigid benzodiazepine chimeric scaffolds.11.