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The tetrasaccharide hapten released from the glycopeptidolipid (GPL) antigen of Mycobacterium aviumserovar 20 has been characterized as O-(2-O-methyl-α-d-rhamnopyranosyl)-(1 → 3)-O-(2-O-methyl-α-l-fucopyranosyl)-(1 → 3)-α-l-rhamnopyranosyl-(1 → 2)-6-deoxy-l-talose. Syntheses are reported of allyl glycosides of the outer disaccharide unit of this hapten, O-(2-O-methyl-α-d-rhamnopyranosyl)-(1 → 3)-2-O-methyl-α-l-fucopyranose, and also of the outer di- and tri-saccharide units of the GPL antigen of M. aviumserovar 14, O-(N-formyl-α-l-kansosaminyl)-(1 → 3)-2-O-methyl-α-d-rhamnopyranose and O-(N-formyl-α-l-kansosaminyl)-(1 → 3)-O-(2-O-methyl-α-d-rhamnopyranosyl-(1 → 3)-2-O-methyl-α-l-fucopyranose. The key steps in the latter synthesis involve the preparation of allyl 4-azido-4,6-dideoxy-3-C-methyl-2-O-methyl-α-l-mannopyranoside as a precursor for the N-formylkansosamine unit, followed sequentially by conversion into and use of a trichloroacetimidate as glycosyl donor for di- and tri-saccharide formation, O-deacylation, reduction, and N-formylation. The allyl glycosides, representative of the haptens from both serovars, have been converted into neoglycoproteins (NGPs) and their serological activities have been compared in the light of the structural relationship between them.

Neoglycoproteins bearing key glycosyl substituents of several glycopeptidolipid antigens of pathogenic Mycobacteriumspecies have been synthesized. Allyl glycosides of the terminal 6-deoxyhexose-containing units of the antigens were prepared, with appropriate ether and ester substituents in place. Ozonolysis of the allyl glycosides was then followed by reductive coupling with ε-amino groups of lysine residues in bovine serum albumin, using sodium cyanoborohydride at pH 7.8. The resulting neoglycoproteins emulated the antigenicity of the native molecule in several serological tests.

The attempted formation of hex-5-enopyranosides from glycosiduronates by the action of Grignard reagents followed by dehydration affords hex-6-enopyranosides or 1,6-anhydrohexopyranoses as major products. 13C nmr spectra of 6,6-di-C-substituted hexose derivatives are compared with those of a number of structurally related compounds. The formation of a hex-5-enopyranoside and the selective cleavage of its glycosidic linkage is illustrated by the synthesis and controlled hydrolysis of methyl 6-O-(6-deoxy-2,3,4-tri-O-methyl-β-L-arabino-hex-5-enopyranosyl)-2,3,4-tri-O-methyl-β-D-glucopyranoside(2).

Methyl α-D-glycopyranosides of 6-deoxy-D-altro-heptose, 6-deoxy-D-manno-heptose, and 6-deoxy-D-talo-heptose have been prepared. Displacements of methyl 2,3,4-tri-O-benzylhexopyranoside 6-trifluoromethanesulfonates with potassium cyanide, followed by reduction of the resulting heptopyranosidurononitriles with diisobutylaluminum hydride, hydrolysis of the imine, further reduction with sodium borohydride, and catalytic O-debenzylation, give the corresponding methyl 6-deoxyheptopyranosides. Configurational change at C-4 of methyl 6-deoxy-7-O-tert-butyldiphenylsilyl-α-D-manno-heptopyranoside to give the taloisomer was effected by oxidation followed by stereoselective reduction. 1H nuclear magnetic resonance data of the glycosides, and gas chromatography of acetylated glycosides of (R)- and (S)-2-butanol serve to establish ring and enantiomeric configurations of the parent sugars when these are encountered as constituents of lipopolysaccharides or extracellular carbohydrate polymers, as in Campylobacterspecies.

An exploration of the synthesis of D-glycero-D-altro-heptose, a constitutent of O antigen chains in lipopolysaccharides from Campylobacterjejuniserotypes O:23 and O:36 led to a study of the 2-trimethylsilylthiazole homologation procedure for heptose synthesis. In contrast to the diastereoselective formation of a 1,2:3,4-di-O-isopropylidene-D-glycero-α-D-galacto-heptopyranose derivative from 1,2:3,4-di-O-isopropylidene-α-D-galacto-hexodialdo-1,5-pyranose, methyl 2,3,4-tri-O-benzyl-D-hexodialdo-1,5-pyranosides with the glucoand mannoconfigurations showed no preference for the formation of compounds with the D-glyceroconfiguration. Attempts to achieve high diastereoselectivity in the conversion of L-glycerointo the D-glyceroisomers by oxidation at C-6 followed by reduction with L-selectride were unsuccessful with the thiazole adducts, but the desired products were formed in similar reactions of methyl 2,3,4-tri-O-benzyl-7-O-tert-butyldimethylsilyl-D-heptopyranosides. The approach to homologation in the altroseries was thwarted by epimerization at C-5 in the attempted formation of methyl 2,3,4-tri-O-benzyl-α-D-altro-hexodialdo-1,5-pyranoside. The successful synthesis of methyl D-glycero-α-D-altro-heptopyranoside from methyl α-D-glucopyranoside was achieved by homologation followed by configurational alteration from the D-glucoto the D-altroseries.

Treatment of methylated degraded leiocarpan A with l,5-diazabicyclo[5.4.0]undec-5-ene and acetic anhydride, followed by mild acid hydrolysis and de-O-acetylation, furnishes 3,4,6-tri-O-methyl-D-mannose and 3,4-di-O-methyl-6-O-(2,3,4-tri-O-methyl-β-D-xylopyranosyl)-D-mannose. The characterization of the methylated disaccharide provides evidence for the site of attachment and anomeric configuration of the D-xylopyranose end groups in the parent polysaccharide.

Two methylated disaccharides, methyl [methyl 4-O-(2,3,4,6-tetra-O-methyl-α-D-glucopyranosyl)-2,3-di-O-methyl-β-D-glucopyranosid]uronate (9) and methyl 6-O-(methyl 2,3,4-tri-O-methyl-α-D-galactopyranosyluronate)-2,3,4-tri-O-methyl-β-D-glucopyranoside (15) have been synthesized and used as model compounds for the study of the base-catalyzed β-elimination of 4-O-substituted hexopyranosiduronates without degradation of exposed reducing sugars and of the selective acid hydrolysis of hex-4-enopyranosiduronates.

Acetylated derivatives (3and 10) of the disaccharides 6-O-β-D-glucopyranosyl-3-O-mesyl-D-glucose and 3-deoxy-6-O-β-D-glucopyranosyl-D-ribo-hexose have been synthesized. The parent disaccharides have been degraded to give 2-deoxy-5-O-β-D-glucopyranosyl-D-erythro-pentose (4) which has been characterized as the methylated disaccharide alditol.

6-O-β-D-Glucopyranosyl-3-O-methyl-D-glucose (4) has been synthesized as a model com pound for regions of branching in polysaccharides. Alkaline degradation of the disaccharide affords an epimeric pair of O-glycosyl metasaccharinic acids which have been characterized by reduction to 3-deoxy-6-O-β-D-glucopyranosyl-D-ribo-hexose (6) and 3-deoxy-6-O-β-D-glucopyranosyl-D-arabino-hexose (7). Alkaline degradation of the branched β-D-glucan from Sclerotiumrolfsiifollowed by reduction of the derived metasaccharinic acids furnishes 3-deoxy-D-ribo-hexose (8), 3-deoxy-D-arabino-hexose (9), and the two disaccharides (6and 7).