Sheila Payne

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 reaction of glutaraldehyde with tissue lipids

Abstract Portions of mouse brain, kidney and liver were fixed with glutaraldehyde and the lipids were then extracted with chloroform methanol. Comparison of the extracted lipids with those from similar portions of the same unfixed tissues by thin layer chromatography showed the absence of phosphatidyl ethanolamine in the extract from the fixed tissues. Acid hydrolysis of the fixed, extracted tissue liberated free fatty acids suggesting that the phosphatidyl ethanolamine had been fixed to the tissue proteins.

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.

THE QUANTITATIVE SEPARATION AND ESTIMATION BY THIN-LAYER CHROMATOGRAPHY OF LIPIDS IN NERVOUS TISSUE.

Abstract Lipids from brain tissue have been estimated densitometrically after separation on thin-layer chromatograms. Standard error on five determinations on three different days for lipids present in large amounts is 2%, but on lipids present in smaller amounts the standard error is sometimes as much as 10%.

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.

Effects of non‐ionic surfactants that modify experimental tuberculosis on lipase activity of macrophages

1 Six series of non‐ionic surface active polyethylene glycol ethers, whose effects on experimental tuberculosis have previously been correlated with their polyoxyethylene chain lengths, were examined for their influence on the activity of a lipase present in homogenates of normal mouse peritoneal macrophages. The surfactants are concentrated in the lysosomes of macrophages—a cell type in which the host‐parasite confrontation takes place. A preparation of soy bean oil was used as triglyceride substrate; and hydrolysis at pH 4·5 was compared in the presence and absence of surfactant, the products of hydrolysis being assayed by photodensitometry of thin‐layer chromatograms. 2 The compounds with short polyoxyethylene chains inhibited the release of fatty acid, compared with surfactant‐free standard, more than did those with long chains; and some of the latter showed actual enhancement of release. Accumulation of monoglyceride was observed in the presence of six of the seven long‐chained compounds, but with none of the seven short‐chained compounds. 3 The similarity between this correlation of chain length of the surfactants with their effect on macrophage lipase activity, and the known correlation of their chain length with their effect on experimental tuberculosis, suggests a possible connection. How this connection might relate to the mechanism of the varying effects on tuberculosis is briefly discussed.

The preparation, resolution, and phosphorylation of some benzyl ethers of myo-inositol: Intermediates for the synthesis of myo-inositol phosphates of the phosphatidylinositol cycle

Abstract The syntheses of the following chiral compounds are described: 1 d -2,3,6-tri-, 1 d -2,4,5-tri-, 1 d -2,5,6-tri-, 1 d -1,2,3,4-tetra-, 1 d -1,2,3,6-tetra-, 1 d -1,2,4,5-tetra-, and 1 d -2,3,5,6-tetra- O -benzyl- myo -inositol; and 1 d -2,5,6-tri- O -benzyl-1- O - p -methoxybenzyl- and 1 d -2,3,5,6-tetra- O -benzyl-1- O - p -methoxybenzyl- myo -inositol. The absolute configurations were established by reference to 1 d -5,6-di- O -methyl- myo -inositol prepared from known 1 d -1,2,4-tri- O -benzyl-5,6- O -isopropylidene- myo -inositol. The preparation of the meso -derivative 2,4,5,6-tetra- O -benzyl- myo -inositol is also described. Several of the benzyl ethers were converted into protected phosphate esters by phosphitylation with bis(benzyloxy)diisopropylaminophosphine or bis(2-cyanoethoxy)diisopropylaminophosphine and subsequent oxidation with m -chloroperoxybenzoic acid. On treatment with sodium iodide in acetone, the syrupy octabenzyl esters of 2,5-di- O -benzyl- myo -inositol 1,3,4,6-tetrakisphosphate and 1 d -2,6-di- O -benzyl- myo -inositol 1,3,4,5-tetrakisphosphate were converted into the crystalline tetrasodium salts of the corresponding tetrakis(benzyl phosphates). These salts are useful compounds for hydrogenolysis to give myo -inositol tetrakisphosphates of the phosphatidylinositol cycle since phosphate migration would not be expected to occur. 1 d -3,6-di- O -octyl- myo -inositol and its racemate were prepared and each showed liquid crystalline behaviour on heating.

The preparation and phosphorylation of 2,5- and 1D-2,6-di-O-benzyl-myo-inositol.

1,3,4,6-Tetra-O-allyl-myo-inositol was converted into the 2,5-di-O-benzyl- and 2,5-di-O-p-methoxybenzyl ethers, and the products were deallylated to give the 2,5-di-O-benzyl (and p-methoxybenzyl) ethers of myo-inositol, which were converted into the mono-O-isopropylidene derivatives. Both the 2,5-di-O-benzyl ether and its mono-O-isopropylidene derivative were converted into the crystalline octa(2-cyanoethyl) ester of 2,5-di-O-benzyl-myo-inositol 1,3,4,6-tetrakisphosphate. (+-)-1,3,4,5-Tetra-O-allyl-myo-inositol was converted into (+-)-2,4-di-O-benzyl-myo-inositol which gave a separable mixture of the 1,6- and 5,6-O-isopropylidene derivatives. The 1,6-O-isopropylidene derivative was resolved via (-)- and (+)-omega-camphanates and was also converted into (+-)-2,6-di-O-benzyl-1,5-di-O-p-methoxybenzyl-myo-inositol, which was resolved via the (-)-omega-camphanates. The 5,6-O-isopropylidene derivative and 1,3-di-O-allyl-myo-inositol were converted into (+-)-1,3-di-O-allyl-2,6-di-O-benzyl-myo-inositol, which was resolved as the (-)-omega-camphanates. 1D-1,3,4,5-Tetra-O-allyl-myo-inositol and the above described, relevant diaste reoisomers were converted into 1D-2,6-di-O-benzyl-myo-inositol which gave the syrupy octabenzyl ester of 1D-2,6-di-O-benzyl-myo-inositol 1,3,4,5-tetrakisphosphate.

The allylation of dibutylstannylene derivatives of myo-inositol

Abstract Reaction of myo -inositol or a mixture of racemic 1,4-, 1,6-, and 4,5-di- O -allyl- myo -inositol in acetonitrile with dibutyltin oxide and allyl bromide in the presence of tetrabutylammonium bromide gave, as the major products, a readily separable mixture of 1,3,4,6- and 1,3,4,5-tetra- O -allyl- myo -inositol together with small proportions of penta- O -allyl- myo -inositols and 1,3,5-tri- O -allyl- myo -inositol (from myo -inositol). Parallel results were obtained when crotyl bromide was used. When 3 equiv. of dibutyltin oxide were used with myo -inositol or 1 equiv. with the mixture of di- O -allyl derivatives, 1,3,4-tri- O -allyl- myo -inositol was the major product. When 2 equiv. of dibutyltin oxide were used, myo -inositol gave a complex mixture of mono-, di-, and tri- O -allyl derivatives which was fractionated after conversion into the O -isopropylidene derivatives. Racemic 1,3,4,5-tetra- O -allyl- myo -inositol was resolved via the (−)-ω-camphanates.

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.