The synthesis of protected 5-azido-5-deoxy-D-glucononitriles as precursors of glycosidase inhibitors

Abstract

The successful syntheses of 5-azido-2,3,4,6-tetra-O-benzyl-5-deoxy-~-glucononitrile and 2,3,4,6-tetra-0-benzyl-5-deoxy-5-trifluoroacetarnido-D-glucononitrile starting from D-glucose are described. Unsuccessful attempts were made to convert these two compounds into a protected 5-amino-5-deoxy-D-glucononitrile and to subsequently cyclize them to an amidine analogue of glucose as a possible glycosidase inhibitor. On dCcrit des synthkses rCalisables des 5-azido-2,3,4,6-tCtra-0-benzyl-5-dCsoxy-et 2,3,4,6-tttra-0-benzyl-5-dCsoxy-5-trifluoroacCtamido-D-glucononitriles ?I partir du D-glucose. On a essay6 sans succks de transformer ces deux compos6s en un ~-amino-5-d6soxy-~-glucononitrile et Cventuellement de les cycliser en une amidine analogue du glucose qui aurait pu &tre tvaluCe cornrne inhibiteur de la glycosidase.Mots cle's : synthkse, amino-sucres, inhibiteurs de la glycosidase.[Traduit par la revue]

Synthesis of a Glucose‐Derived Tetrazole as a New β‐Glucosidase Inhibitor. A New Synthesis of 1‐Deoxynojirimycin

“…The specific rotation of 20, the IR and the 'H-NMR spectra are in keeping with the published data, with the exception of the ddat 3.8 ppm, for which we find J = 2.4 and 9.2 Hz and not J = 2 and 6.8 Hz [28]. are two crystallographically independent molecules (I and 11, Fig.…”

“…The major side product was the 2,5-anhydro-~-glucononitrile 21 (1 0 YO) [22]. Monitoring the reaction by TLC indicated the formation of an intermediate, less polar then the tosylate or the tetrazole, which was isolated and identified as the known [28] The conformations of lS1.5, 18, and 19 may (partially) be deduced and compared, based on the vicinal coupling constants (see the Table). For the o-gluco-alcohol 13, large values of J(2,3) and J(4,5), a small value of J(3,4),…”

ChemInform Abstract: Synthesis of a Polyhydroxylated Tetrahydro‐4H‐1,2,3‐triazolo[1,5‐a]azepin, a Higher Homolog of “Nojiritriazole”, and of a Related C‐Disaccharide.

“…Our current work on iminosugars and imino-C-glycosyl compounds led us to explore the synthetic potential of 5azido-5-deoxy-D-glucofuranose derivative 4, 6 a little studied nojirimycin equivalent. 7 In particular, we examined the reaction of 4 with alkynyl organometallic reagents.…”

“…Compound 4 was prepared from 5-azido-5-deoxy-3,6-di-O-benzyl-1,2-O-isopropylidene-a-D-glucofuranose 8 as described by Withers et al 6,8 Ethynylation of the azidohemiacetal 4 was achieved with in-situ generated ethynylcerium(III) dichloride 4 and afforded the octynitol 5 as a single stereoisomer in high yield (Scheme 1). The configuration of the newly created stereocenter at C-3 was unambiguously established to be R at the stage of the bicyclic product 6.…”

Synthesis of a Polyhydroxylated Tetrahydro-4H-1,2,3-triazolo[1,5-a]azepin, a Higher Homolog of "Nojiritriazole", and of a RelatedC-Disaccharide

“…Compound 4 was prepared from 5-azido-5-deoxy-3,6-di-O-benzyl-1,2-O-isopropylidene-a-D-glucofuranose 8 as described by Withers et al 6,8 Ethynylation of the azidohemiacetal 4 was achieved with in-situ generated ethynylcerium(III) dichloride 4 and afforded the octynitol 5 as a single stereoisomer in high yield (Scheme 1). The configuration of the newly created stereocenter at C-3 was unambiguously established to be R at the stage of the bicyclic product 6.…”