Robert Conant

The Allyl Group for Protection in Carbohydrate Chemistry, Part 14.1 Synthesis of 2, 3-Di-O-Methyl-4-O-(3, 6-Di-O-Methyl-β-D-Glucopyranosyl)-L-Rhamnopyranose (and its α-Propyl Glycoside): A Haptenic Portion of the Major Glycolipid from Mycobacterium Leprae

Abstract 3, 6-Di-O-methyl-d-glucose was prepared via 5-O-allyl-1, 2-O-isopropylidene-3-O-methyl-αd-glucofuranose and was converted into 2, 4-di-O-acetyl-3, 6-di-o-methyl-dD-glucopyranosy 1 chloride. Condensation of the chlorosugar with methanol or allyl 2, 3-O-isopropylidene-α-l-rhamnopyranoside gave the corresponding crystalline β-glycbsides. The allyl 4-O-(2,4-di-O-acetyl-3, 6-di-O-Tnethyl-β-dD-glucopyranosyl)-2, 3-O-isopropylidene-α-l-rhamnopyranoside was converted into the title compounds and into crystalline 2, 3-di-O-acetyl-4-O-(2, 4-di-O-benzyl-3, 6-di-O-methyl-β-d-glucopyranosyl)-l-rhamnopyranosyl chloride which should serve as an intermediate for the synthesis of the trisaccharide portion of the major glycolipid of Mycobacterium leprae.

The allyl group for protection in carbohydrate chemistry. Part 21. (±)-1,2 : 5.6- and (±)-1,2 : 3,4-di-O-isopropylidene-myo-inositol. The unusual behaviour of crystals of (±)-3,4-di-O-acetyl-1,2,5,6-tetra-O-benzyl-myo-inositol on heating and cooling: a ‘thermosalient solid’

Racemic 1,2-O-isopropylidene-myo-inositol was converted into a mixture of 1,2 : 5,6-, 1,2 : 3,4-, and 1,2 : 4,5-di-O-isopropylidene-myo-inositols which were resolved by g.l.c. The 1,2 : 4,5- and 1,2 : 5,6- isomers were isolated from the mixture as benzoate derivatives. Allylation of the mixed isomers allowed the separation of all three allyl ethers by column chromatography and these were converted into the corresponding di-O-allyl-myo-inositols. 1,4-Di-O-allyl-myo-inositol was converted into 1,4-di-O-allyl-5,6-O-isopropylidene-myo-inositol on kinetic acetonation. Removal of the allyl groups from 5,6-di-O-allyl-1,2 : 3,4-di-O-isopropylidene-myo-inositol gave pure 1,2 : 3,4-di-O-isopropylidene-myoinositol which gave the known 1,2,3,4-tetra-O-benzyl-myo-inositol. Crystals of the diacetate of 1,2,5,6 tetra-O-benzyl-myo-inositol showed interesting ‘jumping’ behaviour on heating and cooling.

Synthesis of propyl 4-O-(3,6-di-O-methyl-β-d-glucopyranosyl)-2,3-di-O-methyl-α-d-rhamnopyranoside☆

Abstract Partial hydrolysis of allyl 2,3:4,6-di- O -isopropylidene-α- d -mannopyranoside gave allyl 2,3- O -isopropylidene-α- d -mannopyranoside which was converted into allyl 2,3- O -isopropylidene-α- d -rhamnopyranoside by reduction of the 6- O -tosyl derivative with lithium aluminium hydride. Condensation of allyl 2,3- O -isopropylidene-α- d -rhamnopyranoside with 2,4-di- O -acetyl-3,6-di- O -methyl-α- d -glucopyranosyl chloride in the presence of mercury(II) cyanide gave the crystalline β-linked disaccharide which was converted into the title compound.

Synthesis of 3-O-(6-deoxy-6-sulpho-α-D-glucopyranosyl)-1,2-di-O-hexadecanoyl-L-glycerol, ‘sulphoquinovosyl diglyceride’

3-O-(2,3,4-Tri-O-benzyl-6-O-tosyl-α-D-glucopyranosyl)-1,2-O-isopropylidene-L-glycerol was treated with potassium thioacetate and the product was hydrolysed with base to give the corresponding 6-deoxy-6-thioderivative which on oxidation with iodine gave the crystalline disulphide. The isopropylidene groups were hydrolysed and the product was acylated with hexadecanoyl chloride in pyridine to give crystalline bis-[3-O-(2,3,4tri-O-benzyl-6-deoxy-α-D-glucopyrancsyl)-1,2-di-O-hexadecanoyl-L-glycerol]-6,6-disulphide. Oxidation of this compound with 3-chloroperbenzoic acid and subsequent hydrogenolysis of the benzyl groups gave the title compound with properties similar to those of a sample prepared by hydrogenation of the natural ‘sulphoquinovosyl diglyceride.’

The Allyl Group for Protection in Carbohydrate Chemistry. 13. The N-Allylbenzylamino Group for Protection in the Amino-Sugar Series

Abstract Derivatives of 2-benzamido-2-deoxy-D-glucose can be converted2 in good yield, into the 2-N-allylbenzylamino derivatives via the 2-N-allylbenzamido derivatives. The N-allylbenzylamino group is a protected amino function which can be readily converted2 into the benzylamino and acylamino functions and we now show other uses for this protecting group in the chemistry of the amino-sugars.

The allyl group for protection in carbohydrate chemistry. Part 20. Synthesis of 1L-1-O-methyl-myo-inositol [(+)-bornesitol] by resolution of (±)-1,2,4-tri-O-benzyl-myo-inositol

Racemic 1,2,4-tri-O-benzyl-myo-inositol was prepared by two new routes from (±)-1,4-di-O-benzyl-5,6-O-isopropylidene-myo-inositol, one route involving the crystalline intermediate (±)-1-O-allyl-3,6-di-O-benzyl-4,5-O-isopropylidene-myo-inositol. Oxidation of the latter and (±)-1,2,4-tri-O-benzyl-5,6-O-isopropylidene-myo-inositol with acetic anhydride-dimethyl sulphoxide gave the corresponding ketones, which were reduced with sodium borohydride to give the starting alcohols in good yield, thus providing suitable routes for the synthesis of isotopically labelled material. Racemic 1,2,4-tri-O-benzyl-5,6-O-isopropylidene-myo-inositol was resolved using (–)-ω-camphanic acid chloride to give, readily and in high yield (86%), the ω-camphanate of 1D-1,2,4-tri-O-benzyl-5,6-O-isopropylidene-myoinositol, which was converted into 1L-1-O-methyl-myo-inositol [(+)-bornesitol] and 1D-1,2,4,5,6-penta-O-benzyl-myo-inositol which had previously been obtained by hydrolysis of perbenzylated galactinol.

The allyl group for protection in carbohydrate chemistry. Part 19. The coupling of allyl 2,3-di-O-methyl-4-O-(3,6-di-O-methyl-β-D-glucopyranosyl)-α-L-rhamnopyranoside to bovine serum albumin. Preparation of a diagnostic reagent for antibodies to the major glycolipid of Mycobacterium leprae(the leprosy bacillus) in human sera

Epoxidation of allyl 4-O-(2,4-di-O-benzyl-3,6-di-O-methyl-β-D-glucopyranosyl)-2,3-di-O-methyl-α-L-rhamnopyranoside and subsequent alkaline hydrolysis of the epoxide and hydrogenolysis of the benzyl groups gave 2′,3′-dihydroxypropyl 2,3-di-O-methyl-4-O-(3,6-di-O-methyl-β-D-glucopyranosyl)-α-L-rhamnopyranoside which was cleaved with sodium metaperiodate to give the corresponding formylmethyl glycoside. Two other routes to the latter compound, via allyl 2,3-di-O-methyl-4-O-(3,6-di-O-methyl-β-D-glucopyranosyl)-α-L-rhamnopyranoside, were also developed. The formylmethyl glycoside was coupled to bovine serum albumin using ‘reductive amination’ in the presence of sodium cyanoborohydride to give a glycoconjugate useful for the serodiagnosis of antibodies to the major glycolipid of Mycobacterium leprae in the sera of leprosy patients. 5′,6′-Dihydroxyhexyl and 10′,11′-dihydroxyundecyl 3,6-di-O-methyl-β-D-glucopyranosides were also prepared as intermediates for the synthesis of the 4-formylbutyl and 9-formylnonyl glucosides respectively which are also suitable for coupling to bovine serum albumin by the ‘reductive amination’ technique.

Conversion of the N-benzylacetamido group into the acetamido group by autoxidation in potassium t-butoxide–dimethyl sulphoxide

The N-benzylacetamido group is rapidly converted into the acetamido group at 20 °C by the action of molecular oxygen in a solution of potassium t-butoxide in sulphoxide and a general route to acetylated amines by the alkylation of N-bnzylacetamide and N-debenzylation by the above method is proposed.

The allyl group for protection in carbohydrate chemistry. 17. Synthesis of propyl O-(3,6-di-O-methyl-β-D-glucopyranosyl)- (1→4)-O-(2,3-di-O-methyl-α-L-rhamnopyranosyl)-(1 → 2)-3-O-methyl-α-L-rhamnopyranoside: the oligosaccharide portion of the major serologically active glycolipid from Mycobacterium leprae☆☆☆

Abstract Allyl 4- O -benzyl-α-L-rhamnopyranoside was converted into allyl 4- O -benzyl-3- O -methyl s - α - L -rhamnopyranoside and this was condensed with 2,3,4-tri- O -acetyl-α-L-rhamnopyranosyl chloride to give a disaccharide derivative which was converted into allyl 4- O -benzyl-2- O -(2,3- O -isopropylidene-α-L-rhamnopyranosyl)-3- O -methyl-α-L-rhamnopyranoside. This disaccharide derivative was condensed with 2,4-di- O -acetyl-3,6-di- O -methyl-α-D-glucopyranosyl chloride to give a trisaccharide derivative which was converted into the title compound. This compound represents the oligosaccharide portion of the major serologically active glycolipid from Mycobacterium leprae which is required to prepare a synthetic diagnostic agent for leprosy infection at an early stage and to investigate the specificities of monoclonal antibodies directed towards the glycolipid.

The allyl group for protection in carbohydrate chemistry. Part 18. Allyl and benzyl ethers of myo-inositol. Intermediates for the synthesis of myo-inositol trisphosphates

Racemic 1,2:4,5-di-O-isopropylidene-myo-inositol was converted into racemic 1,2,4-tri-O-benzyl-myo-inositol, 1,2,4-tri-O-p-methoxybenzyl-myo-inositol and 2,4,5-tri-O-benzyl-myo-inositol using allyl groups for ‘temporary’ protection. The benzyl ethers are required as intermediates for the synthesis of the ‘second messenger,’ inositol 1,4,5-trisphosphate and its metabolite, inositol 1,3,4-trisphosphate. 1,2,3,4-Tetra-O-benzyl-myo-inositol, and its two monoallyl and monoprop-1-enyl ethers, were also prepared as model compounds for phosphorylation studies of the vicinal 5,6-diol system which occurs in 1,2,4-tri-O-benzyl-myo-inositol.