Palladium−Charcoal-Catalyzed Reduction of Tri-O-acetyl-β-l-Fucopyranosyl Cyanide:  A Route to Small Cluster Oligosaccharide Mimetics (SCOMs)

Abstract

[reaction: see text] Synthesis of glycosyl cyanides was optimized with a new catalyst system. Reduction of tri-O-acetyl-beta-L-fucopyranosyl cyanide with Pd-hydrogen, in the presence of Ac(2)O and Boc(2)O, gave N-protected-mono- and -di-(2,3,4-tri-O-acetyl-beta-L-fucopyranosylmethyl)-amines, which allow for the syntheses of small cluster oligosaccharide mimetics of fucopyranosylomethyl-substituted ureas. From di-(2,3,4-tri-O-acetyl-beta-L-fucopyranosylmethyl) amine was also prepared a carbamoyl chloride as a potentially useful synthon for preparation of more complex C-glycosidic conjugates.

Synthetic Approaches to Small Cluster Oligosaccharide Mimetics

“…When per-O-acetyl-α-or β-D-glucopyranose was treated with excess TMS-CN and 0.1 molar equiv of HgBr 2 in nitromethane for 2 days in the absence of Hg(CN) 2 , the major product was the 1,2-cyanoethylidene derivative 14 in 59% yield, along with only 5% of the preferred cyanide 15, and about 28% of starting material (Scheme 4) [54][55][56], similar to the results of Coxon and Fletcher with Hg(CN) 2 [44]. When we increased the amount of HgBr 2 to at least 0.5 equiv, the cyanoethylidene intermediate rearranged into the desired per-O-β-D-glucopyranosyl cyanide 15 in 51% yield starting from per-Oacetyl-β-D-glucopyranose, or 65% yield from purified cyanoethylidene intermediate 14, within 1 day.…”

“…The omission of Hg(CN) 2 was crucial. This suggested that rearrangement required the assistance of a mercuric isocyanide complex in conjunction with the existence of equilibrium between the exo-cyanoethylidene 14 and the acetoxonium intermediate [55,56].…”

“…However, the elimination of the unstable glycosyl bromides as intermediates was a distinct advantage. We decided to investigate the use of HgBr 2 , as a milder catalyst for this reaction (Schemes 4,5) [54][55][56].…”

“…One versatile approach to glycosyl cyanide modification, with which we have considerable experience, is catalytic reduction [54,55,[66][67][68][69]. Hydrogenation of per-Oacetyl-β-L-fucopyranosyl cyanide 17 with catalytic palladium-charcoal in the presence of acetic anhydride (Ac 2 O) gave the isolated O-N-acetyl migrated products 27 and 28 in 32% and 23% yields, respectively (Scheme 8) [54,55,[67][68][69].…”

“…Hydrogenation of per-Oacetyl-β-L-fucopyranosyl cyanide 17 with catalytic palladium-charcoal in the presence of acetic anhydride (Ac 2 O) gave the isolated O-N-acetyl migrated products 27 and 28 in 32% and 23% yields, respectively (Scheme 8) [54,55,[67][68][69]. The yield for the Nlinked aminodisaccharide 28 decreased to 9% without the presence of Ac 2 O.…”