Synthesis of a series of disaccharides of potential immunological significance
Creators: name: Bebault, Gwendolyn Mary
Publisher: name: University of British Columbia
Year: 2010

description: Disaccharides are useful for immunological studies, the identification of isolated polymer fragments, and studies on model compounds but few have been synthesized. The syntheses of four new disaccharides of the 4-0-glycopyranosyl-L-rhamnopyranose series namely 4-0-g-D-glucopyranosyl--L-rhamnopyranose (15), 4-0-a-L-rhamnopyranosyl-L-rhamnopyranose (26), 4-0--a-D-mannopyranosyl-L-rhamnopyranose (38), and 4-0-8-D-mannopyranosyl-L--rhamnopyranose (56) are reported. The selectively substituted aglycon used for all the members of this series was methyl 2,3-0-isopropylidene-a-L-rhamnopyranoside (3) prepared by acetalation of methyl a-L-rhamnopyranoside and purified through crystalline methyl 4-0-acetyl-2,3-0-isopropylidene-a-L-rhamnopyranoside (2). Compound 2_ was deacetalated to give methyl 4-0-acetyl-a-L-rhamno--pyranoside which served as a key intermediate for the preparation of the standards 2,3-di-O-methyl-L-rhamnose and 4-deoxy-L-erythritol. Disaccharide J15_ was prepared in an overall yield of 55% based on the aglycon by first condensing 2,3,4,6 - tetra-O-acetyl-a-D-glucopyranosyl bromide with 3^ in the presence of mercuric cyanide in acetonitrile to give crystalline methyl 2,3-C-isopropylidene-4-0-(2,3,4,6-tetra-0-acetyl-g-D--glucopyranosyl)-a-L-rhamnopyranoside (10) in 80% yield based on 3_. Since the isopropylidene group of 1_0 could not be acetolyzed it was removed with trifluoroacetic acid to give methyl 4-0-(2,3,4,6-tetra-0-acetyl-B-D-gluco--pyranosyl)-a-L-rhamnopyranoside (11) . Acetolysis of n_ gave crystalline 1,2,3-tri-0-acety1-4-0- (2,3,4,6-tetra-0-acetyl-i3-D - glucopyranosyl)-a-L--rhamnopyranose (14). Deacetylation of 1_1_ gave the methyl glycoside of the disaccharide which, as for the subsequent disaccharides, was subjected to methylation and periodate oxidation studies to confirm the 1,4 linkage. An improved method for the quantitation of periodate oxidation degradation products is described. Deacetylation of 1_4_ gave L5_ which was reduced to give 4-0-B-D-glucopyranosyl-L-rhamnitol which upon acetylation gave crystalline 1,2,3,5-tetra-C-acetyl-4-0-(2,3,4,6-tetra-O-acetyl-g-D-glucopyran--osyl)-L-rhamnitol. In an analogous manner disaccharides 26_ and 38 were prepared in overall yields of 60 and 55% based on the aglycon by condensing 2,3,4-tri--O-acetyl-a-L-rhamnopyranosyl bromide and 2,3,4,6-tetra-O-benzoyl-a-D--mannopyranosyl bromide respectively with _3. The deblocking procedures paralleled those of the D-gluco analog. Disaccharide 26_ was characterized as crystalline methyl 2,3-di-0-acetyl-4-0-(2J3,4-tri-C-acetyl-a-L-rhamno--pyranosyl)-ct-L-rhamnopyranoside, 1,2,3-tri-O-acetyl-4-0-(2,3,4-tri-O-acetyl--a-L-rhamnopyranosyl)-a-L-rhamnopyranose, and 1,2,3,5-tetra-C-acetyl-4-0--(2,3,4-tri-0-acetyl-a-L-rhamnopyranosyl)-L-rhamnitol. Disaccharide 38^ was crystalline and was also characterized as crystalline 1,2,3-tri-c7-acetyl-4--0-(2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl)-a-L-rhamnopyranose and l,2,3,5-tetra-0-acetyl-4-0-(2,3,4,6-tetra-O-acetyl-a-D-mannopyranosyl)-L--rhamnitol. A combined reduction acetylation procedure for the 2,3-di-O--methyl-L-rhamnose obtained from methylated 26 produced a boron-containing derivative of 2,3-di-O-methyl-L-rhamnitol. Proton magnetic resonance spectroscopy was used to substantiate the configuration of the linkage in these disaccharides. A general method for the synthesis of 3-D-mannopyranosides was developed to synthesize disaccharide 56^. This was done by preparing 4,6- -di-0-acetyl-2,3-0-carbonyl-a-D-mannopyranosyl bromide (44) through sequential formation of the carbonate, acetolysis, and bromination of methyl 4 ,.6-0-benzylidene-a-D-mannopyranoside. Bromide 44 was condensed with methanol to give crystalline methyl 4,6-di-0-acetyl-2,3-0-carbonyl-g--D-mannopyranoside (45) in 87% yield. Deacylation of 45_ gave methyl 3-D--mannopyranoside which was characterized as its crystalline isopropylate and peracetate. Disaccharide 5_6_ was prepared in an overall yield of 50% based on the aglycon by condensing 44 with 3_ in the presence of silver oxide in chloroform. The deblocking procedures were similar to those for the previous disaccharides. Acetolysis of the disaccharide intermediates in the sequence was profoundly influenced by the presence of the cyclic carbonate group. Disaccharide 5_6_ was characterized as crystalline methyl 4-0-8-D-mannopyranosyl-a-L-rhamnopyranoside isopropylate and 1,2,3-tri-O--acety1-4-0-(2,3,4,6-tetra-0-acetyl-B-D-mannopyranosyl)-a-L-rhamnppyranose.