The use of 2-deoxy-2-trichloroacetamido-d-glucopyranose derivatives in syntheses of hyaluronic acid-related tetra-, hexa-, and octa-saccharides having a methyl β-d-glucopyranosiduronic acid at the reducing end

Expeditious and stereocontrolled syntheses are reported of β-d-GlcpNAc-(1 → 4)-[β-d-GlcpA-(1 → 3)-β-d-GlcpNAc-(1 → 4)]n-β-d-GlcpA-(1 → OMe), where n = 1, 2, and 3, which represent structural elements of the extracellular polysaccharide hyaluronic acid. Condensation of 4,6-O-benzylidene-3-O-chloroacetyl-2-deoxy-2-trichloroacetamido-α-d-glucopyranosyl trichloroacetimidate with methyl (4-methoxyphenyl 2,3-di-O-benzoyl-β-d-glucopyranosid)uronate gave the disaccharide derivative 9, which was demethoxyphenylated and imidoylated to afford the pivotal disaccharide trichloroacetimidate 7. Condensation of 7 with methanol followed by O-dechloroacetylation gave the acceptor 8. Coupling of 7 with 8 gave the tetrasaccharide derivative 4. O-Dechloroacetylation of 4 followed by condensation with imidate 7 afforded hexasaccharide 5, which was transformed into octasaccharide 6 by a similar two-step procedure. Subsequent O-dechloroacetylation, transformation of the N-trichloroacetyl groups into N-acetyl, debenzylidenation, and saponification of 4–6 afforded the tetra- (1), hexa- (2), and octa-saccharide (3) derivatives in high yields, as their sodium salts.