Approach toward a generic treatment of Gram-negative infections: Synthesis of haptens for catalytic antibody mediated cleavage of the interglycosidic bond in lipid A

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-delta-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-delta-lactam (17) coup-led to the carrier protein bovine serum albumin.