J.M. Webber

Fluorinated carbohydrates : Part I. 3-deoxy-3-fluoro-d-glucose1

Abstract Treatment of 1,2:5,6-di- O -isopropylidene-3- O -toluene- p -sulphonyl-α- d -allofuranose with tetrabutylammonium fluoride in acetonitrile gave 3-deoxy-3-fluoro-1,2:5,6-di- O -isopropylidene-α- d -glucofuranose ( 6 ) in 74% yield. The structure of 6 was established by a multistage conversion into known 3-deoxy-3-fluoro- d -xylose. Graded hydrolysis of 6 with acid gave 3-deoxy-3-fluoro-1,2- O -isopropylidene-α- d -glucofuranose ( 7 ), and total hydrolysis gave 3-deoxy-3-fluoro- d -glucose (15–18% overall yield from d -glucose). 3-Deoxy-3-fluoro- d -glucose gave a crystalline β-tetra-acetate and was reconverted into 7 on treatment with acetone in the presence of acid, followed by graded hydrolysis with acid. In a similar manner, 1,2- O -cyclohexylidene-3-deoxy-3-fluoro-α- d -glucofuranose was obtained.

Observations on esterification reactions

Abstract The rate constants for the esterification of a series of alcohols with acetic anhydride at 25° have been determined. No rate-enhancement effect attributable to intramolecular hydrogen-bonding was observed, in contrast to esterifications with acid chlorides and sulphonyl chlorides in pyridine. With acetic anhydride in pyridine, 1,4:3,6-dianhydro- D -glucitol is selectively acetylated at position 2. If pyridine hydrochloride is also present in the mixture, selective esterification occurs at position 5. The mechanisms of these and related reactions is considered. cis -5-Amino-2-phenyl-1,3-dioxan is more rapidly esterified with acetic anhydride in pyridine than is the trans -isomer; parallel results have been observed in the cyclohexane series.

Diastereoisomeric forms of methyl 4,6-O-benzylidene-2,3-di-O-methyl-α-d-gluco- and α- and β-d-galactopyranoside

Abstract Treatment of methyl 2,3-di- O -methyl-α- d -glucopyranoside with benzylidene bromide, toluene, potassium tert -butoxide, and tert -butanol gave two diastereoisomeric 4,6- O -benzylidene derivatives ( A and B ). The complete conversion A → B was effected with carbon tetrachloride-hydrogen chloride. Only diastereoisomer B was formed on acid-catalysed benzylidenation. Closely parallel results were obtained on benzylidenation of methyl 2,3-di- O -methyl-α- and β- d -galactopyranoside under basic conditions. The possible conformations of the benzylidene derivatives are considered on the basis of n.m.r. spectroscopic data. At equilibrium in the acid-catalysed benzylidenation of methyl α- d -galactopyranoside the only product present is the 4,6- O -benzylidene derivative, m.p. 168–170°, [α] d + 144° in chloroform. In the early, kinetically-controlled, stages of the reaction, small amounts of the diastereoisomeric 3,4- O -benzylidene derivatives were detected.

Some structural studies of brea gum (an exudate from Cercidium australe jonhst.)

Abstract The gum exudate (brea gum) from the leguminous tree Cercidium australe contains residues of l -arabinose, d -xylose, d -glucuronic acid, and 4- O -methyl- d -glucuronic acid, in the approximate molar ratios of 1,7:6,3:1,9:0,9. Autohydrolysis of the gum afforded (chromatographic identification) xylobiose (and homologues), 2- O - and 4- O -(α- d -glucopyranosyluronic acid)- d -xylose, and 2- O -(4- O -methyl-glucopyranosyluronic acid)- d -xylose. The principal, neutral components of the methylated gum were 3- O - and 2,3,4-tri- O -methyl- d -xylose; by chromatographic methods, 2,3-di- O -methyl- d -xylose and - l -arabinose, and a tri- O -methylarabinose were also detected. After reduction, the acidic products from the methylated gum gave, inter alia , 3,4-di- O -methyl- d -glucose and 2,3,4-tri- O -methyl- d -glucose (chromatographic identification). The major structural features of brea gum appear to be a β-(1 → 4)-linked d --xylan backbone [possibly containing some (1 → 2)-linkages] that is heavily 2-substituted by short branch-chains containing residues of d -xylose (and l -arabinose) and d -glucuronic acid, in which both types of residue may be terminal. Approximately one-third of the uronic acid is present as the 4-methyl ether, and, in the purified polysaccharide, a similar proportion of the acid residues is lactonised. Supporting evidence for these features was obtained by periodate-oxidation studies of the carboxyl-reduced polysaccharide.

Diphenylmethylation of carbohydrate hydroxyl groups by the reaction with diazo(diphenyl)methane

Abstract Diphenylmethylation of carbohydrate hydroxyl groups may be effected by the thermal reaction with diazo(diphenyl)methane in the absence of catalysts. Migration of the labile ester groups of methyl 2,3,4-tri- O -acetyl-α- d -glucopyranoside and 3- O -benzoyl-1,2- O -isopropylidene-α- d -glucofuranose does not occur during diphenylmethylation by this procedure. The diphenylmethyl group may be readily removed by catalytic hydrogenolysis, and is sufficiently acid-stable to enable the selective hydrolysis of acetal groups. Its use as an O-4 protecting-group and as a non-participating O-2 protecting-group in α-glycoside synthesis has been demonstrated in syntheses of methyl 2,3,6-tri- O -methyl-α- d -glucopyranoside and kojibiose octa-acetate, respectively.

The addition of dichloromethylene to unsaturated sugars

Abstract Addition of dichloromethylene to 3,4,6-tri- O -methyl- d -glucal gave a single product that was tentatively identified, by stereochemical considerations as, 1,5-anhydro-2-deoxy-1,2- C -(dichloromethylene)-3,4,6-tri- O -methyl- d - glycero - d - ido -heptitol(1), and was characterised, after demethylation, as the tribenzoate 3 . 3-Deoxy-1,2:5,6-di- O - isopropylidene-α- d - erythro -hex-3-enofuranose reacted with dichloromethylene to give 3-deoxy-3,4- C -(dichloromethylene)-1,2:5,6-di- O -isopropylidene-α- d -galactofuranose ( 6 ), which was then converted by mild hydrolysis with acid into the 1,2- O -isopropylidene derivative ( 8 ). Reduction of compound 1 and 6 with lithium aluminium hydride gave the corresponding cyclopropyl derivatives, 4 and 7, respectively.

Regioselective monoalkylations of the vicinal cis-diol group in mannopyranosides using diaryldiazoalkanes-tin(II) chloride

Abstract Highly regioselective monoalkylations of the cis -2,3-diol group in mannopyranosides can be achieved with diaryldiazoalkanes in the presence of catalytic amounts of tin(II) chloride. With diazo(diphenyl)methane ( 1 ), its 4,4′-dimethyl ( 2 ) and 4,4′-dichloro ( 3 ) derivatives, and 9-diazofluorene ( 5 ), methyl 4,6- O -benzylidene- α - d -mannopyranoside gave high yields of the respective 3-diarylmethyl ethers. By contrast, methyl 4,6- O -isopropylidene- α - d -mannopyranoside ( 11 ) gave mainly the 3-[bis(4-methylphenyl)methyl] derivative with 2 , approximately equal amounts of the 2- and 3-ethers with 1 and 3 , and mainly the 2-ether with 5 . With diazo[bis(4-methoxyphenyl)]methane, 11 gave only the 3-ether (61%).

Further observations on the acid-catalysed benzaldehyde-glycerol reaction

Abstract The proportions of cis - and trans -5-hydroxy-2-phenyl-1,3-dioxan and cis - and trans -4-hydroxymethyl-2-phenyl-1,3-dioxolan in acid-catalysed, equilibrated, O -benzylidene-glycerol mixtures are critically dependent on solvent and temperature. In carbon tetrachloride, elevation of temperature increases the proportion of dioxolan derivatives and, at a given temperature, diminishing concentration increases the proportion of the cis -1,3-acetal at the expense of the trans -isomer. At equilibrium in dimethyl sulphoxide, the trans -1,3-acetal is preponderant. On acid-catalysed benzylidenation of glycerol under homogeneous conditions ( N , N -dimethylformamide), the 1,2-acetals form rapidly in the initial, kinetic phase, and the 1,3-acetals are preponderant at equilibrium. A rationalisation of some of these observations is presented.

Derivatives of 2-hydroxy-1,4-oxathiane and 2-hydroxymorpholine. A new class of sugar☆

Abstract Application in sequence of periodate oxidation, borohydride reduction, tosylation, and treatment with sodium sulphide to methyl α- l -rhamnopyranoside affords (2 R ,6 S )-2-methoxy-6-methyl-1,4-oxathiane. Likewise, methyl 6- O -trityl-α- d -glucopyranoside and 1,6-anhydro-β- d -glucopyranose were converted into 1,4-oxathiane derivatives. Acid-catalysed equilibration of (2 R ,6 S )-2-methoxy- and (2 R ,6 S )-2-acetoxy-6-methyl-1,4-oxathiane affords, in each case and in contrast to structurally related tetrahydropyran derivatives, a mixture containing ca. 70% of the cis (diequatorial) isomer. Replacement of sodium sulphide by methanolic ammonia in the above reaction sequence results in the conversion of the rhamnoside into (2 R ,6 S )-2-methoxy-6-methylmorpholine. The behaviour of the free amine and the N -acetyl derivative on acid hydrolysis is described. At low temperature, the n.m.r. spectrum of the N -acetyl derivative is consistent with the existence of geometrical isomers.

Mode of decomposition of chloro- and fluoro-formates of some carbohydrates and related compounds

Abstract It has been established that thermal and catalytic decomposition of certain alkyl haloformates affords dialkyl carbonates in addition to alkyl halides. Pyridine(or quinoline)-catalysed decomposition of ethyl and cyclohexyl chloroformate and ethyl fluoroformate affords high yields of alkyl halides, but cyclohexyl fluoroformate yields a significant proportion of dialkyl carbonate. In compounds containing the structural unit O·C-C·O·CO·Hal, chloroformates yield alkyl chlorides and dialkyl carbonates, whereas with fluoroformates, dialkyl carbonates are the sole products. The halo-formates of the following compounds have been examined: cyclohexanemethanol, 2-(hydroxymethyl)tetrahydropyran, 1,2:3,4-di- O -isopropylidene-α- D -galactose, 1,2:3,4-di- O -isopropylidene- DL 0xylitol, and trans -2-methoxycyclohexanol. Quinoline-catalysed decomposition of trans -1,2-bis(fluoroformyloxy)cyclohexane affords mainly the cyclic carbonate of cyclohexane- trans -1,2-diol, together with small proportions of cyclohexa-1,3-diene and an unidentified, volatile product.