Synthesis of C-xylopyranosyl- and xylopyranosylidene-spiro-heterocycles as potential inhibitors of glycogen phosphorylase

C-(2-Deoxy-d-arabino-hex-1-enopyranosyl)-oxadiazoles: synthesis of possible isomers and their evaluation as glycogen phosphorylase inhibitors

“…The rather scarce literature of 1-C-hetaryl pyranoid glycals 45e48 offers possibilities for both strategies and neither of them seems superior. 47 Since the 2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl cyanide 49 23 was shown to be a common precursor toward each isomer of C-glucopyranosyloxadiazoles 40 (24) were probed to get the 1-cyanoglucal 25 (Scheme 1). The latter method proved to be more efficient both in terms of purity of the product and overall yields (compare yields under conditions a and b in Scheme 1 taking into account that 24 can be obtained almost quantitatively 49 ).…”

“…Xylopyranosylidene-spiro-hydantoins, the first compounds investigated in this series, proved practically inactive. 23 Xylopyranosylidene-spiro-isoxazolines and oxathiazoles, 24 having the most potent aglycones of the glucopyranosyl series, 25e27 remained also ineffective. 24 Xylopyranosyl counterparts of N-(b-Dglucopyranosyl)-1,2,3-triazoles (e.g., 8 in Chart 1) as well as analogous derivatives of 5-thio-xylose and their oxidized variants (sulfoxides and sulfones) showed also negligible or no inhibition against RMGPb.…”

“…23 Xylopyranosylidene-spiro-isoxazolines and oxathiazoles, 24 having the most potent aglycones of the glucopyranosyl series, 25e27 remained also ineffective. 24 Xylopyranosyl counterparts of N-(b-Dglucopyranosyl)-1,2,3-triazoles (e.g., 8 in Chart 1) as well as analogous derivatives of 5-thio-xylose and their oxidized variants (sulfoxides and sulfones) showed also negligible or no inhibition against RMGPb. 28 Very recently, C-b-D-xylopyranosyl-heterocycles were synthesized (e.g., 21 and 22), and among them only the 2-naphthyl substituted 1,2,4-triazole derivative 21 had modest activity towards RMGPb.…”

“…28 Very recently, C-b-D-xylopyranosyl-heterocycles were synthesized (e.g., 21 and 22), and among them only the 2-naphthyl substituted 1,2,4-triazole derivative 21 had modest activity towards RMGPb. 24 Other studies with N-b-D-glucopyranosyl-pyrimidines 15,17 2e7…”

C-Glycosyl 1,2,4-triazoles: Synthesis of the 3-β-d-glucopyranosyl-1,5-disubstituted and 5-β-d-glucopyranosyl-1,3-disubstituted variants

“…C-Glycosyl 1,2,4-triazoles are an even more uncommon type [15][16][17][18] and only in recent years has progress been made in this field with the syntheses of 3-glycopyranosyl-5-substituted-1,2,4-triazoles as glycogen phosphorylase inhibitors for potential antidiabetic use. [19][20][21][22][23][24] As a continuation of our efforts in the above syntheses, the preparation of trisubstituted Cglycopyranosyl 1,2,4-triazoles was envisaged to generate molecules for structure-activity relationships of glycogen phosphorylase inhibitors and also for other potential biological applications. From the three possible isomeric structures (Scheme 1) some examples of the 3-glycosyl-4,5-disubstituted-1,2,4-triazoles (I) were already described, 21 therefore, this work has focused on the 3-β-D-glucopyranosyl-1,5-disubstituted (II) and 5-β-D-glucopyranosyl-1,3-disubstituted (III) counterparts.…”