Abstract
A chemo-enzymatic approach combining an enzymatic regioselective hydrolysis of peracetylated N-acetyl-alpha-D-glucosamine (1) with a mild controlled acyl migration led to 2-acetamido-2-deoxy-1,3,6-tri-O-acetyl-alpha-D-glucopyranose, which was further used in a glycosylation reaction in the synthesis of beta-O-naphtylmethyl-N-peracetylated lactosamine.
Candida rugose lipase (CRL) immobilized on octyl-agarose and modified by covering it with polyethyleneimine was the best catalyst in terms of activity, stability and regioselectivity in the hydrolysis of 1, producing the deacetylation in C-6 in 95% overall yield. Other immobilized lipases were not specific or with a very low activity towards the hydrolysis of 1.
An acyl chemical migration by incubation of the deacetylated C-6 derivative at pH 8.5, 4 degrees C, and 10-20% acetonitrile permitted to obtain up to 75% overall yield of the 4-OH derivative product. This molecule was successfully applied in a glycosylation reaction to get the peracetylated U-D-lactosamine and finally, the peracetyl-beta-O-naphtylmethyl-lactosamine derivative in 20% overall yield. (C) 2007 Elsevier B.V. All rights reserved.