Synthesis of alpha-Kdo-(2----4)-Kdo disaccharide derivatives and their conjugation with a protected form of GLA-60, a biologically active analog of a lipid A subunit.

A variety of the protected O-[(3-deoxy-alpha-D-manno-2-octulopyranosyl)onic acid]-(2----4)-3-deoxy-D-manno-2-octulosonic acid [alpha-Kdo-2(2----4)-Kdo] derivatives have been synthesized starting from methyl [2-(trimethylsilyl)ethyl 4,5,7,8-tetra-O-acetyl-3-deoxy-alpha-D-manno-2-octulopyranosid] onate. Some of these were conjugated with a protected form of a bacterial lipid A subunit-analog (GLA-60) having beneficial immunopharmacological activity, namely benzyl 2-[(3R)-3-(benzyloxy-methoxy)tetradecanamido]-2-deoxy-4-O- (diphenoxyphosphinyl)3-O-[(3R)-3-tetradecanoyloxytetradecanoyl+ ++]-beta -D-glucopyranoside.