Approach Toward a Generic Treatment of Gram-Negative Infections: Synthesis of Haptens for Catalytic Antibody Mediated Cleavage of the Interglycosidic Bond in Lipid A

Abstract

In order to develop a generic treatment for infections with Gram-negative bacteria, we developed a synthesis of 2-acylamino-deoxynojirimycin derivatives (17, 18, 19 and 20), which will be used as haptens for raising catalytic antibodies capable of hydrolyzing the interglycosidic bond in the lipid A moiety of endotoxins. A key intermediate in the preparation of compounds 17, 18, 19 and 20 is 3,4,6-tri-O-benzyl-2-[(benzyloxycarbonyl)amino]-2-deoxy-D-glucono-δ-lactam (6), which was prepared from known 3,4,6-tri-O-benzyl-2-[(benzyloxycarbonyl)amino]-2-deoxy-D-glucosamine (1) in four steps in 47% overall yield. Antibodies were generated against 2-[(6-aminohexanoyl)amino]-2-deoxy-D-glucono-δ-lactam (17) coupled to the carrier protein bovine serum albumin.