Alain Veyrières

A mild procedure for the regiospecific benzylation and allylation of polyhydroxy-compounds via their stannylene derivatives in non-polar solvents

The reactions of benzyl and allyl bromides on the stannylene derivatives of polyhydroxy-compounds, which normally proceed only at insignificant speed in refluxing benzene solution, are greatly accelerated in the presence of quaternary ammonium halides. These conditions were tested on benzyl β-D-galactopyranoside (1) and ten derivatives, (2)–(11), which were benzylated, allylated, or acetalated. In such a collection may be found all the possible arrangements, except one, of two, three, or four hydroxy-groups on a β-D-galactopyranoside ring. Regiospecific substitution in good yield was observed on nine of the starting polyols. Benzylation in this way of benzyl 2,3-di-O-benzyl-α-D-glucopyranoside only gave the 6-O-benzyl ether in 80% yield, a great improvement over the reaction in NN-dimethylformamide, which has no preparative value. The same new method allows a smooth preparation of the monomethoxymethyl ethers of glycols. The preparations and synthetic uses of the stannylene derivatives of γ-and Iµ-glycols are reported for the first time.

Synthesis of O-β-D-galactopyranosyl-(1→4)-O-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→3)-D-mannose, a postulated trisaccharide of human erythrocyte membrane sialoglycoprotein

Monoallylation of tributylstannylated benzyl 6-O-trityl-α-D-mannopyranoside (3) was efficiently catalysed by tetrabutylammonium bromide to give the 3-O-(4) and 2-O-(5) allyl ethers in 62 and 15% yields, respectively. Compound (4) was converted into crystalline benzyl 3-O-allyl-2,4-di-O-benzyl-α-D-mannopyranoside (10), which was then isomerized, allylated, and hydrolysed to give benzyl 6-O-allyl-2,4-di-O-benzyl-α-D-mannopyranoside (11). This compound was condensed with the oxazoline (12), derived from D-lactosamine, to give the protected trisaccharide (13) in 9% yield. Removal of the protecting groups gave the free trisaccharide β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-D-Man (15). The carbohydrate sequence of this trisaccharide has been postulated in some membrane glycoproteins and will be tested for its li blood group activity.

Complete regiospecificity in the benzylation of a cis-diol by the stannylidene procedure

While conventional monobenzylation of benzyl 6-O-allyl-2-O-benzyl-α-D-galactopyranoside (1) gives a four component mixture, treatment of the OO′-dibutyl-stannylidene derivative of (1) with benzyl bromide provides only the 3-O-benzyl ether (2) in 66% isolated yield.

Blood-group li-active oligosaccharides. Synthesis of a tetrasaccharide, a β-(1 → 3) dimer of N-acetyl-lactosamine

Condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide, followed by de-O-acetylation, acetonation, O-benzylation, and acidic hydrolysis afforded the 3′,4′-diol (5) derived from N-acetyl-lactosamine. This compound was selectively glycosylated at the 3′-position by the oxazoline (7) derived from lactosamine to give the protected tetrasaccharide (8) in 52% yield. Removal of the protecting groups gave the free tetrasaccharide β-D-Galp-(1 → 4)-β-D-GlcpNAc-(1 → 3)-β-D-Galp-(1 → 4)-D-GlcpNAc (9), a β-(1 → 3) dimer of N-acetyl-lactosamine. This structure has been found in various glycolipids isolated from erythrocyte membranes and could be recognized by several anti-iantisera.

Synthesis of 4-methylumbelliferyl 1,2-cis-glycosides

Abstract Condensation of 4-methylumbelliferone (7-hydroxy-4-methylcoumarin) with 1,2,3,4,6-penta- O -acetyl-β- d -glucopyranose ( 1 ) and 1,2,3,4,6-penta- O -acetyl-β- d -galactopyranose ( 9 ) in the presence of zinc chloride gave, respectively, a mixture of α-( 2 ) and β- d -glucopyranosides ( 3 ) in the ratio of 2:3, and a mixture of α- d -galactopyranoside ( 10 ), β- d -galactofuranoside, and β- d -galactopyranoside ( 11 ) in the ratio of 10:17:23. The proportion of 1,2- cis -glycosides could be slightly increased by treating 1 and 9 with the O -trimethylsilyl derivative of 4-methylumbelliferone in the presence of stannic chloride. Condensations of the sodium salt of 4-methylumbelliferone with 2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyl chloride, 2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl chloride, and 2,3,4,6-tetra- O -acetyl-α- d -mannopyranosyl bromide in hexamethylphosphoric triamide gave, respectively, pure 2 , pure 10 , and a mixture of α- and β- d -mannopyranosides in the ratio of 1:3, with much better yields. O -Deacetylation of 2 , 3 , 10 , and 11 , followed by platinum-catalyzed oxidation, afforded the corresponding 4-methylumbelliferyl d -glycopyranosiduronic acids.

Syntheses of 3-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-galactopyranose (“lacto-N-biose II”) and 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-galactopyranose

Abstract 3- O -(2-Acetamido-2-deoxy-β- d -glucopyranosyl)-α- d -galactopyranose ( 10 , “Lacto- N -biose II”) was synthesized by treatment of benzyl 6- O -allyl-2,4-di- O -benzyl-β- d -galactopyranoside with 2-methyl-(3,4,6-tri- O -acetyl-1,2-dideoxy-α- d -glucopyrano)[2,1- d ]-2-oxazoline ( 5 ), followed by selective O -deallylation, O -deacetylation, and catalytic hydrogenolysis. Condensation of 5 with benzyl 6- O -allyl-2- O -benzyl-α- d -galactopyranoside, followed by removal of the protecting groups, gave 10 and a new, branched trisaccharide, 3,4-di- O -(2-acetamido-2-deoxy-β- d -glucopyranosyl)- d -galactopyranose ( 27 ).

Synthesis of a branched pentasaccharide: one of the core oligosaccharides of human blood-group substances

Condensation of the lactosamine-derived per-O-acetyl oxazoline (6) with the trisaccharide derivative (1) followed by removal of the protecting groups, gave the branched pentasaccharide, β-D-Galp(1→3)-β-D-GlcpNAc(1→3)-[β-D-Galp(1→4)-β-D-GlcpNAc(1→6)]-D-Gal (4); the reduced form of this compound has been previously reported as present among the degradation products of soluble Lea-active glycoprotein from ovarian cysts.

Stannylene derivatives in glycoside synthesis. Application to the synthesis of the blood-group B antigenic determinant

Condensation of benzyl 2,6-di-O-benzyl-3,4-O-dibutylstannylene-α-D-galactopyranoside (9) with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of stannic chloride occurred at the 3- and 4-positions to give the branched trisaccharide (11) with two β-anomeric linkages. A (1→3)-linked ortho ester (13) was selectively obtained by reaction of compound (9) with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl chloride in NN′N″-hexamethylphosphorotriamide; when the solvent was dichloroethane, a mixture of the ortho ester (13) and a branched product (15) with two ortho ester residues was obtained in a 2 : 1 ratio. 2,3,4,6-Tetra-O-benzyl-α-D-galactopyranosyl chloride selectively reacts at the 3-position of compound (9) in the presence of lithium iodide in NN′N″-hexamethylphosphorotriamide to give a 9 : 1 mixture of the α- and β-(1→3)-linked disaccharides (16) and (18) in 82% yield. The latter conditions were applied to the synthesis of the blood-group B antigenic determinant starting from the 2-O-allyl stannylene compound (10). Coupling of 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide under bromide-ion catalysis occurred at the 2-position of disaccharide (26) in 32% yield. Hydrogenation afforded the free trisaccharide (29), α-L-Fuc-(1→2)-[α-D-Gal-(1→3)]-D-Gal.

Studies in oligosaccharide chemistry. Part 8. Synthesis of lacto-N-triose I, a core chain trisaccharide of human blood-group substances

Condensation of 4,6-di-O-acetyl-1,2-dideoxy-2′-methyl-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-glucopyranoso[2,1-d]-Δ2′-oxazoline (4) with benzyl 6-O-allyl-2,4-di-O-benzyl-α-D-galactopyranoside (5) in the presence of toluene-p-sulphonic acid gave a protected trisaccharide (6) in 84% yield. Removal of the protecting groups gave the free trisaccharide β-D-Gal-(1 → 3)-β-D-GlcNAc-(1 → 3)-D-Gal (10), identical in properties with ‘Lacto-N-triose-I,’ a product of acidic hydrolysis of carbohydrates from human milk and blood-group substances. The carbohydrate sequence of the trisaccharide (10) is representative of the ‘core’ portion of blood-group substances.

Mercaptolyse du 2-acétamido-3-O-(D-1-carboxyéthyl)- 2-désoxy-D-glucose (acide N-acétylmuramique)

Abstract Treatment of 2-acetamido-3- O -( D -1-carboxyethyl)-2-deoxy- D -glucose ( N -acetylmuramic acid) with ethanethiol and hydrochloric acid gave a mixture of the acyclic dithioacetal ( 2 ) and the corresponding internal ester. After substitution of the hydroxyl and carboxyl groups, the dithioacetal was transformed into the dimethyl acetal ( 5 ) by treatment with mercuric oxide and boron trifluoride etherate in anhydrous methanol. Removal of the O -acetyl group with sodium methoxide afforded 2-acetamido-2-deoxy-5,6- O -isopropylidene-3- O -[ D -1-(methoxycarbonyl)-ethyl]- D -glucose dimethyl acetal ( 6 ), but the reaction was very slow and led to partial decomposition