Use of N-Pivaloyl Imidazole as Protective Reagent for Sugars

Abstract

N -Pivaloyl imidazole was prepared and used as a selec- tive protective reagent of different monosaccharides (D-glucose, D-mannose, D-galactose, 2-acetamido-2-deoxy-D-glucose and 2- acetamido-2-deoxy- β -D-glucopyranosyl azide) and lactose. A variety of pivalates were obtained with moderate or good regiose- lectivity. Esters are important protecting groups in carbohydrate chemistry. 1-6 Selective acylation in carbohydrates is pos- sible by the combination of the different reactivity of the hydroxy groups with the use of hindered carboxylic acid chlorides (such as pivaloyl chloride and diphenylacetyl chloride 7 ) or the use of less reactive esterifying reagents that transfer acyl groups (such as N -acyl imidazoles, 3,8-12 benzoyl cyanide, 13,14 3-acylthiazolidine-2-diones and 3- acyl-5-methyl-1,3,4-thiadiazole-2(3 H )-thiones 15-17 ). Piv- aloyl esters with their great steric hindrance can be formed very selectively with pivaloyl chloride in pyridine at low temperature. 18 Additional advantages of this protecting group are, first, their slow reactivity with NH 3 in methanol or guanidine, that allows the selective removal of the widely used acetates in the presence of pivaloates, 19-21 and, second, the decrease tendency to give orthoesters during Koenigs-Knorr glycosidation. 22-25 More recently enzymic regioselective deacylations of pivaloyl monosac- charide derivatives with esterases from mammaliam sera have been reported. 26 The ability of pivaloyl chloride to acylate sugars selectively has been previously exploited in the synthesis of various pivaloylated monosaccharide gly- cosides (methyl α -D-glucopyranoside, 27 methyl α -D-