Chemistry of bacterial endotoxins. Part 6. Synthesis of allyl 5-O-(α-D-mannopyranosyl)-(3-deoxy-α-D-manno-oct-2-ulopyranosid) onic acid and of allyl 5-O-(α-D-mannopyranosyl)-(3-deoxy-α-D-manno-oct-2-ulopyranosid)onic acid 4-phosphate and their copolymers with acrylamide

Abstract

A mixture of methyl (allyl-7,8-O-cyclohexylidene-3-deoxy-α-, and -β-D-manno-oct-2-ulopyranosid)onates (3 : 1) was prepared from methyl 2,4,5,7,8-penta-O-acetyl-3-deoxy-α-D-manno-oct-2-ulopyranosonate in 3 steps and the anomers were separated by chromatography. Sequential treatment of the α-glycoside with dibutyltin oxide and tert-butyldimethylsilyl chloride gave the corresponding 4-O-tert-butyldimethylsilyl 1,5-lactone. Transformation of the lactone with MeONa to the corresponding ester, was accompanied by partial migration of the silyl group and yielded a 2:1 mixture of the 4-O-, and 5-O-tert-butyldimethylsilyl derivatives which were separated by chromatography. Condensation of the former with 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl bromide in 1,2-dichloroethane in the presence of N,N,N′,N′-tetramethylurea and under silver trifluoromethanesulphonate catalysis afforded a 71% yield of the protected α-linked disaccharide. The silyl group was removed selectively with tetrabutylammonium fluoride, whereafter deprotection by conventional methods produced the unprotected title disaccharide. The alcohol obtained after the removal of the silyl group was treated with bis(trichloroethyl) phosphorochloridate to afford the corresponding phosphotriester which, after deprotection, gave the phosphorylated title disaccharide. Both were copolymerized with acrylamide. ¹H NMR revealed that the phosphorylated disaccharide formed a complex with Ca²⁺ involving Man 4-O, 6-O, and oxygen atoms of the phosphate group.