Synthesis of β-D-GlcA-(1 → 3)-β-D-Gal disaccharides with 4- and 6-sulfate groups and 4,6-disulfate groups

Article abstract of DOI:10.1016/0008-6215(91)84027-C

The sodium salts of the 6-sulfate 7, the 4-sulfate 10, and the 4,6-disulfate 12 of benzyl 3-O-(β-D glucopyranosyl uronate)-β-D-galactopyranoside (5) have been synthesized. Methyl (2,3,4-tri-O-acetyl-1 bromo-1-deoxy-α-D-glucopyran)uronate (1) was coupled with benzyl 2-O-benzoyl-4,6-O-benzylidene-β-D galactopyranoside (2) to yield 3. The benzylidene acetal of 3 was hydrolyzed to give benzyl 2-O-benzoyl-3-O [methyl (2,3,4-tri-O-acetyl-β-D-glucopyranosyl)uronate]-β-D-galactopyranoside (4). Compound 4 was utilized as a key intermediate to prepare the sulfated disaccharides 7, 10, and 12. Direct sulfation of 4 with sulfur trioxide-trimethylamine for 2 days yielded the 6-sulfate 6. The 4,6-disulfate II was accessible by running the reaction under the same conditions for 14 days. The 4-sulfate 9 was obtained after protecting the 6-OH group of 4 by reaction with benzoyl imidazole to give the 6-benzoate 8, followed by sulfation under vigorous conditions. Treatment of the protected compounds 4, 6, 9, and 11 with aqueous sodium hydroxide in tetrahydrofuran gave the unprotected 5, 7, 10, and 12, respectively. The sodium salts of the 6-sulfate 7, the 4-sulfate 10, and the 4,6-disulfate 12 of benzyl 3-O-(β-D-glucopyranosyl uronate)-β-D-galactopyranoside (5) have been synthesized. Methyl (2,3,4-tri-O-acetyl-l-bromo-1-deoxy- α-D-glucopyran)uronate (1) was coupled with benzyl 2-O-benzoyl-4,6-O-benzylidene-β-D-galactopyranoside (2) to yield 3. The benzylidene acetal of 3 was hydrolyzed to give benzyl 2-O-benzoyl-3-O-[methyl (2,3,4-tri-O-acetyl-β-D-glucopyranosyl)uronate] β-D-galactopyranoside (4). Compound 4 was utilized as a key intermediate to prepare the sulfated disaccharides 7, 10, and 12. Direct sulfation of 4 with sulfur trioxide-trimethylamine for 2 days yielded the 6-sulfate 6. The 4,6-disulfate 11 was accessible by running the reaction under the same conditions for 14 days. The 4-sulfate 9 was obtained after protecting the 6-OH group of 4 by reaction with benzoyl imidazole to give the 6-benzoate 8, followed by sulfation under vigorous conditions. Treatment of the protected compounds 4, 6, 9, and 11 with aqueous sodium hydroxide in tetrahydrofuran gave the unprotected 5, 7, 10, and 12, respectively.