Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The application of the 2-(chloroacetoxymethyl)benzoyl (CAMB) group to the O-protection of position 2 in glycosyl donors is described. Saponification of the phthalide and subsequent chloroacetylation of 2-(hydroxymethyl)benzoic acid (1) gave 2-(chloroacetoxymethyl)benzoic acid (2). Treatment of 2 with thionyl chloride afforded the acyl chloride 3. Acylation of O-2 of 1,3,4,6-tetra-O-acetyl-α-D-glucopyranose (4a), galactopyranose (4b) and of the amino group of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-D-glucopyranose (4c) afforded the fully protected pyranose derivatives 5a-c in high yields. Compounds 5a and 5b were converted with HBr in acetic acid into the corresponding 2-O-CAMB-protected bromides 6a, b in excellent yields. Silver trifluoromethanesulfonate promoted glycosylation of the latter with 2-hydroxyethyl benzoate yielded the β-glycosides 8a (74%) and 8b (69%). Direct activation of the glucosamine derivative 5c with ferric chloride gave the glucoside 8c (54%). Furthermore, the galactosyl bromide 6b was coupled with methyl 2,3,4-tri-O-benzoyl-β-D-glucopyranoside (11) affording the 2′-O-CAMB-protected methyl glycoside disaccharide 12 (63%). Similarly, condensation of the glucosyl bromide 6a with 4a gave the β-(1→2)-linked disaccharide 13 (45%). Treatment of compounds 8a and 13 with thiourea resulted in the deblocked glycosides 9a and 14. Similar deprotection of 8b gave 2-benzoyloxyethyl 3,4,6-tri-O-acetyl-β-D-galactopyranoside (9b) and the 2-O-[2-(hydroxymethyl)benzoyl] derivative 10. Reaction of 8c with thiourea afforded solely the dechloroacetylated glucoside 9c.
Type of Medium: