Jocelyne Alais

Regioselective mono-o-alkylation of disaccharide glycosides through their dibutylstannylene complexes

Abstract Allyl β- N -Acetyllactosaminide, methyl β- N -phthalogllactosaminide. and methyl β-lactoside give with high selectivity and good yields the corresponding 3′-O-allyl derivatives by reaction of their dibutylstannylene complexes with allyl bromide and tetrabutylammonium bromide.

New accesses to l-iduronyl synthons

(PhS)3CLi adds with a total l-ido selectivity onto 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-dialdose 2, opening the way to the most efficient preparation of 1,2,4-tri-O-acetyl-3-O-benzyl-l-iduronyl synthon 8. Alternatively, in view of combinatorial syntheses, aldehyde 2 allows a good access to vinylic l-ido and d-gluco synthons which may be converted into uronic acid by a sequence involving a new aldehyde oxidation by m-CPBA in aqueous solution.

STEREOSELECTIVITY CONTROL IN ANOMERIC O-ALKYLATION. APPLICATION TO THE SYNTHESIS OF C2 SYMMETRIC GLYCOCONJUGATES

Abstract Tetrabutylammonium salts strongly influence the stereoselectivity of O-anomeric alkylation and allows to shift from β to α selectivity. Allyl glucosaminide 7 prepared in this way, was used to synthesize the new type of C2 symmetric neoglycoconjugates 1a-c.

Synthesis of an octasaccharide fragment of the polylactosamine series by a blockwise approach

Abstract Block synthesis of an octasaccharide, β-(1-3) linked tetramer of N -acetyllactosamine, is reported. Intermediate di- and tetrasaccharides were converted either into trichloroacetimidates acting as glycosyl donors or into vicinal diols acting as glycosyl acceptors.

Block synthesis of a hexasaccharide hapten of i blood group antigen

Abstract Block synthesis of a hexasaccharide, β-(1→3) linked trimer of N -acetyllactosamine, is reported. This proved to be a potent inhibitor of anti-i antibodies.

Further definition of the size of the blood group-i antigenic determinant using a chemically synthesised octasaccharide of poly-N-acetyllactosamine type

In earlier studies, the minimum structure which inhibited the binding of anti-i to an i-active glycoprotein was the linear trisaccharide, beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-D-Gal. There was an increasing hierarchy of inhibitory activities in the linear tetrasaccharide, beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-beta-D-Galp-(1----4)-beta-D -GlcNAc , its methyl beta-glycoside, and in the methyl beta-glycoside of the hexasaccharide. The linear octasaccharide methyl beta-glycoside in this series is approximately only half as active as the hexasaccharide methyl beta-glycoside. Analyses by high resolution 1H-n.m.r. of these two oligosaccharides indicated that they have similar conformations in solution, and there is no evidence for the occurrence of inter-molecular interactions which might partially hinder the binding of anti-i to the octasaccharide methyl beta-glycoside. These results are consistent with the size of the i antigen being in the region of a hexasaccharide. It is proposed that the methyl aglycon group of the hexasaccharide methyl beta-glycoside confers an above normal activity by presenting a hydrophobic area for additional contact in the vicinity of the antibody-combining site.

A precursor to the β-pyranosides of 3-amino-3,6-dideoxy-d-mannose (mycosamine)

Abstract S N 2-type reaction of 3- O -(1-imidazyl)sulfonyl-1,2:5,6-di- O -isopropylidene-α- d -glucofuranose with benzoate gave the 3- O -benzoyl-α- d - allo derivative 2 , which was hydrolysed to give the 5,6-diol 3 . Compound 3 was converted into the 6-deoxy-6-iodo derivative 4 which was reduced with tributylstannane, and then position 5 was protected by benzyloxymethylation, to give 3- O -benzoyl-5- O -benzyloxymethyl-6-deoxy-1,2- O -isopropylidene-α- d -allofuranose ( 6 . Debenzoylation of 6 gave 7 , (1-imidazyl)sulfonylation gave 8 , and azide displacement gave 3-azido-5- O -benzyloxymethyl-3,6-dideoxy-1,2- O -isopropylidene-α- d -glucofuranose ( 9 , 85%). Acetolysis of 9 gave 1,2,4-tri- O -acetyl-3-azido-3,6-dideoxy-α,β- d -glucopyranose ( 10 and 11 ). Selective hydrolysis of AcO-1 in the mixture of 10 and 11 with hydrazine acetate (→ 12 ), followed by conversion into the pyranosyl chloride 13 , treatment with N,N -dimethylformamide dimethyl acetal in the presence of tetrabutylammonium bromide, and benzylation gave 3-azido-4- O -benzyl-3,6-dideoxy-1,2- O -(1-methoxyethylidene)-α- d -glucopyranose ( 15 ). Treatment of 15 with dry acetic acid gave 1,2-di- O -acetyl-3-azido-4- O -benzyl-3,6-dideoxy-β- d -glucopyranose ( 16 , 86% yield) that was an excellent glycosyl donor in the presence of trimethylsilyl triflate, allowing the synthesis of cyclohexyl 2- O -acetyl-3-azido-4- O -benzyl-3,6-dideoxy-β- d -glucopyranoside ( 17 , 90%). O -Deacetylation of 17 , conversion of the product into the (1-imidazyl)sulfonic ester, and S N 2 substitution with benzoate gave cyclohexyl 3-azido-2- O -benzoyl-4- O -benzyl-3,6-dideoxy-β- d -mannopyranoside ( 18 ), which was reduced and N -acetylated to give cyclohexyl 3-acetamido-2- O -benzoyl-4- O -benzyl-3,6-dideoxy-β- d -mannopyranoside ( 19 ).