Syntheses of Modified Carbohydrates with Glycosidases: Stereo- and Regiospecific Syntheses of Lactosamine Derivatives and Related Compounds¹

Abstract

Abstract Different lactosamine derivatives, modified in the 2-N- and anomeric positions and suitable as intermediates for synthesis of Lewis-x and related compounds, were prepared with high specificity on a multigram scale directly from lactose, employing different D-glucosamine derivatives as acceptors and the abundant β-D-galactosidase from Bullera singularis as catalyst. Thus, methyl O-β-D-galactopyranosyl-(1→4)-2-azido-2-deoxy-β-D-glucopyranoside, ethyl O-β-D-galactopyranosyl-(1→4)-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside and ethyl O-β-D-galactopyranosyl-(1→4)-2-deoxy-2-(2,2,2-trichloroethoxycarbonylamino)-1-thio-β-D-glucopyranoside were formed in 20-40 % yield as calculated based on added acceptor. The 2-phthalimido derivative was isolated in crystalline form without chromatography (extraction/crystallization procedure). The trisaccharide derivative ethyl O-β-D-galactopyranosyl-(1→4)-O-β-D-galactopyranosyl-(1→4)-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside was also isolated. The corresponding cellobiosamine derivatives were similarly obtained from cellobiose using the same type of catalyst and acceptors. The β-D-galactosidase from bovine testes was found to catalyze the highly specific formation of the β(1→6)-linked derivative ethyl O-β-D-galactopyranosyl-(1→6)-2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside from lactose and ethyl 2-deoxy-2-phthalimido-1-thio-β-D-glucopyranoside. Ethyl O-α-L-fucopyranosyl-(1→4)-2-amino-6-O-benzyl-2-deoxy-1-thio-β-D-glucopyranoside, suitable as an intermediate for preparation of Lewis-a and related compounds, was obtained from p-nitrophenyl α-L-fucopyranoside and 2-amino-6-O-benzyl-2-deoxy-1-thio-β-D-glucopyranoside, employing α-L-fucosidase from bovine testes as catalyst.