Gordon J.F. Chittenden

Synthesis of isothiocyanate-derived mercapturic acids

Twelve mercapturic acids derived from saturated and unsaturated aliphatic and aromatic isothiocyanates were synthesised, by adding isothiocyanate to a solution of N-acetyl-L-cysteine and sodium bicarbonate, in a typical yield of 77%. Isothiocyanates were synthesised first by adding the corresponding alkyl bromide to phthalimide potassium salt. The obtained N-alkyl-phthalimide was hydrazinolysed yielding the alkyl amine, which subsequently was reacted with thiophosgene yielding the isothiocyanate with an overall yield of 16%. Mercapturic acids in urine can serve as a biomarker of intake to determine the health promoting potential of isothiocyanates present in cruciferous vegetables.

Syntheses of (3R,4R,5R,6R)-tetrahydroxyazepane (1,6-dideoxy-1,6-imino-d-mannitol) and (3S,4R,5R,6R)-tetrahydroxyazepane (1,6-dideoxy-1,6-imino-d-glucitol)

Abstract Syntheses of 1,6-dideoxy-1,6-imino- d -mannitol ( d -mannoazepane) ( 1 ) and 1,6-dideoxy-1,6-imino- d -glucitol ( d -glucoazepane) ( 3 ) from d -isoascorbic acid and d -glucono-1,5-lactone, respectively, are described. The key step in both routes involved reductive aminative 1,6-cyclization with retention of configurations to give the corresponding lactams, which were subsequently reduced to afford compounds 1 and 3 in 24 and 28.5%, overall yield, respectively.

Isopropylidenation of d-mannitol under neutral conditions

Abstract Isopropylidenation of d -mannitol ( 2 ) under neutral conditions, by treatment with 2,2-dimethoxypropane in 1,2-dimethoxyethane, is described. 1,2,:5,6-Di- O -isopropylidene- d -mannitol is the main equilibrium product, which does not undergo further subtitution under the conditions used. 1,2:3,4:5,6-Tri- O -isopropylidene- d -mannitol, the other major product, was shown to be derived mainly from initial 3,4-substitution of 2 . The presence of a difunctional ether, of suitable geometry, is a necessary requirement for the reaction. Some mechanistic aspects of the reaction are discussed.

Syntheses of 2-O-methyl-, 3-O-methyl-, and 2,3-di-O-methyl-d-talose and some derivatives thereof

Abstract The title compounds, and some derivatives thereof, have been synthesised from easily accessible benzyl 3-O-benzoyl-4,6-O-benzylidene-β- d -galactopyranoside (4). Treatment of 4 with methyl sulphoxide-phosphorus pentaoxide gave the known ketone 5, which was stereospecifically reduced with neutralised sodium borohydride, without cleavage of the benzoate group, to benzyl 3-O-benzoyl-4,6-O-benzylidene-β- d -talopyranoside (6). Under mild alkaline conditions, 6 was converted into the corresponding 2-benzoate 10. Debenzoylation of 6 gave the diol 7. Methylation of 6, 7, and 10 with diazomethane in the presence boron trifluoride etherate gave the corresponding methylated products in high yield. Removal of the blocking groups by conventional methods gave 2-O-methyl, 3-O-methyl-, and 2,3-di-O-methyl- d -talose. Methylation of 7, with diazomethane in the presence of a catalytic amount of stannous chloride dihydrate showed high specificity to give benzyl 4,6-O-benzylidene-3-O-methyl-β- d -talopyranoside (16, 89%).

Synthesis of 1-deoxy-L-gulonojirimycin (L-guloDNJ) and 1-deoxy-D-talonojirimycin (D-taloDNJ).

Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5-dideoxy-1,5-imino-L-gulitol (L-guloDNJ) and 1,5-dideoxy-1,5-imino-L-talitol (L-taloDNJ) are reported, from D-mannose and D-fructose, respectively. The key steps in both syntheses involved reductive aminative cyclizations. Thus, L-guloDNJ was obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-O-p-toluenesulfonyl-D-mannononitrile with LiAlH(4) in DME to give the protected azasugar which upon hydrolysis with HCl afforded crystalline L-guloDNJ as the HCl salt in 29% overall yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta-D-ribohexulofuranose obtained from D-fructose in six steps, followed by treatment with HCl, afforded L-taloDNJ as an HCl salt in approximately 10% overall yield.

An efficient synthesis of (S)-5-hydroxymethyl-2(5H)-furanone

A three step synthesis of the title compound 1a from D-ribono-1,4-lactone in 48% yield is described. The concept centers on a novel NaHSO3-induced trans-Br-OAc elimination of the readily prepared bromo-acetate mixture 3a,b to the corresponding butenolides 1e and 1f, the former of which, on hydrolysis and purification, yields pure 1a.

Some aspects of the isopropylidenation of d-glucitol under neutral conditions

Abstract Isopropylidenation of d -glucitol ( 1 ) under neutral conditions, by treatment with 2,2-dimethoxypropane in 1,2-dimethoxyethane, has been studied. An improved procedure for the isolation of 1,2:5,6-di- O -isopropylidene- d -glucitol, the main equilibrium product, by direct crystallisation or via the 3,4-dibenzoate is described. Some aspects of the reaction are discussed and compared with results obtained previously from the isopropylidenation of 1 in the presence of zinc chloride.

Synthesis of some trideoxy-d-hexoses and derivatives thereof from d-glucono-1,5-lactone☆

Abstract Enantiospecific syntheses of methyl 2,3,4-trideoxy-α- d - and -β- d -glycero-hexopyranoside (10 and 11) methyl α- d - and β- d -amicetopyranoside (24 and 25), (2S)-1,2-hexanediol (36), (2S)-1,2,6-hexanetriol (37), and some derivatives thereof from d -glucono-1,5-lactone are described.

Decyl and dodecyl β-d-fructofuranosides

Abstract Decyl and dodecyl β- d -fructofuranosides are formed from d -fructose and catalysed by boron trifluoride alcoholates, in admixture with the corresponding α- d anomers and β- d -pyranosides. These were separated by chromatography and each of the products was fully characterized by NMR spectroscopy and as tetrakis(p-nitrobenzoates).

Some aspects of the reaction of methyl 4,6-O-benzylidene-α-D-glucopyranoside 2,3-carbonate with 1-dodecanol : novel non-ionic surfactants

Abstract The reaction of methyl 4, 6-0-benzylidene-α-D-glucopyranoside 2, 3-cyclic carbonate (2) with 1-dodecanol in the presence of a catalytic amount of triethylamine to yield the 2-O-and the 3-O-alkoxycarbonyl esters 5 and 6 is described. Catalytic hydrogenation of 5 and 6 gave the deprotected mono-esters 3 and 4 which are of interest as potential non-ionic surfactants. The corresponding ethoxycarbonyl esters 7 and 8 were also prepared and their possible role as intermediates in the formation of 2 is discussed.