Synthesis of non-glycosidic 4,6’-thioether-linked disaccharides as hydrolytically stable glycomimetics

MARÍA LAURA UHRIG; LASZLO SZILAGYI; KATALIN E. KOVER; OSCAR VARELA

CARBOHYDRATE RESEARCH

Elsevier Science

Año: 2006

0008-6215

Michael addition of 1,2:3,4-di-O-isopropylidene-6-thio-a-D-galactose (2) to 2-propyl 6-O-acetyl-3,4-dideoxy-a-D-glycerohex-3-enopyranosid-2-ulose (1) afforded, as the major diastereoisomer, 2-propyl 6-O-acetyl-3-deoxy-4-S-(6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranos-6-yl)-4-thio-a-D-threo-hexopyranosid-2-ulose (3, 91% yield). Reduction of the carbonyl group of 3, followed by O-deacetylation gave the two epimers 7 (a-D-lyxo) and 8 (a-D-xylo) in a 1:2 ratio. On removal of the protecting groups of 8 by acid hydrolysis, formation of an 1,6-anhydro bridge was observed in the 3-deoxy-4-thiohexopyranose unit (10). The free nonglycosidic thioether-linked disaccharide 3-deoxy-4-S-(6-deoxy-a,b-D-galactopyranos-6-yl)-4-thio-a,b-D-xylo-hexopyranose (11) was obtained by acetolysis of 10 followed by O-deacetylation. A similar sequence starting from the enone 1 and methyl 2,3,4-tri-Obenzoyl-6-thio-a-D-glucopyranoside (12) led successfully to 2-propyl 3-deoxy-4-S-(methyl 6-deoxy-a-D-glucopyranos-6-yl)-4-thio-a-D-lyxo-hexopyranoside (17) and its a-D-xylo analog (19, major product). In this synthetic route, orthogonal sets of protecting groups were employed to preserve the con.guration of both reducing ends and to avoid the formation of the 1,6-anhydro ring.