Thio and seleno sugar esters of dialkylarsinous acids

The syntheses of 2,3,4,6-tetra-O-acetyl-1-S-dimethylarsino-1-thio-β-D-glucopyranose (3), 2,3,4,6-tetra-O-acetyl-1-Se-dimethylarsino-1-seleno-β-D-glucopyranose (4), 1-S-dimethylarsino-1-thio-β-D-glucopyranose (5), and -1-Se-dimethylarsino-1-seleno-β-D-glucopyranose (7) are described. The n.m.r., Raman, and mass-spectral properties of the compounds are given. 3-O-Diethylarsino-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose has also been prepared, but characterized only by n.m.r. spectroscopy.     

Purification and properties of an endo-(1 leads to 3)-beta-D-glucanase from malted barley

3,6-Anhydro-α-D-galactopyranose 1,2-(methyl orthoacetate) and its 4-acetate were synthesized from 2,3,4-tri-O-acetyl-6-O-tosyl-α-D-galactopyranosyl bromide. Condensation of the above-mentioned, acetylated ortho ester with 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose gave 6-O-(2,4-di-O-acetyl-3,6-anhydro-β-D-galactopyranosyl)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose. The same disaccharide derivative was synthesised from 6-O-β-D-galactopyranosyl-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose by mono-O-tosylation followed by treatment with alkali and acetylation.     

Studies of carbohydrate derivatives having the -CH2F function

The following primary sulphonates have been converted into the corresponding deoxyfluoro derivatives by reaction with potassium fluoride in ethylene glycol:1,2:3,4-di-O-isopropylidene-6-O-tosyl α-D-galactopyranose (1), methyl 2,3-O2-isopropyliden-5-O-tosyl-α,β-D-ribofuranoside (2), 1,2:3,4-di-O-methylene-6-O-tosyl-α-D-glucofuranose (3), 3,5-di-O-benzylidene-1,2-O-isopropylidene-6-O-tosyl-α-D-glucofuranose (4), and 1,2:3,5-di-O-isopropylidene-6-O-tosyl-α-D-glucofuranose (5). The yields were generally poor; in the reaction of 1, a major by-product was 6-O-(2-hydroxyethyl)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (11). The reaction of the primary hydroxyl precursor of each of the above tosylates with N2-(2-chloro- 1,1,2-trifluoroethyl)-N,N-diethylamine generally yielded the O-chlorofluoroacetyl derivative; however, 1,2:3,5-di-O-methylene-α-D-glucofuranose (12) was converted into the 6-deoxy-6-fluoro derivative (8). The ¹⁹F resonances of compounds containing the CH₂F moiety fall between φ_C +213 and φ_C +235 p.p.m. The differences between the vicinal¹⁹F-¹H couplings of compounds having the D-gluco and D-galacto configurations clearly reflect the influence of the C-4O-4 substitutents on the populations of the C-5C-6 rotamers. A novel type of noise-modulated, heteronuclear decoupling experiment is described.     

Über die Synthese partiell benzylierter Zucker

1,2:5,6-Di-O-isopropylidene-α-D-allofuranose (1), 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (2), and 1,2.3,4-di-O-isopropylidene-α-D-galactopyranose (3) have been separately treated in pyridine solution with trifluoromethanesulphonic anhydride, 2,2,2-trifluoroethanesulphonyl chloride, and pentaflucrobenzenesulphonyl chloride. Both 1 and 2 afforded the anticipated sulphonic esters. Although 3 also gave the 2,2,2-trifluoroethanesulphonic and pentafluorobenzenesulphonic esters, the reaction with trifluoromethanesulphonic anhydride yielded 6-deoxy-1,2:3,4-di-O isopropylidene-6-pyridino-α-D-galactopyranose trifluoromethanesulphonate.     

Photochemical conversion of sugar dimethylthio-carbamates into deoxy sugars

Protected sugar derivatives having one free hydroxyl group may be deoxygenated at the alcoholic position by ultraviolet irradiation of the corresponding dimethylthiocarbamic esters: a concomitant process leads also to the original alcohol. Thus, on photolysis, the 6-dimethylthiocarbamate (1) or 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (3) gives 6-deoxy- 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (2) together with 3. Likewise, the 4-dimethylthiocarbamate (6) of 1,6-anhydro-2.3-O-isopropylidene-β-D-mannopyranose (8) gives a mixture of the 4-deoxy derivative 7 and the alcohol 8. 3-Deoxy-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranose (10) was obtained by irradiation of 3-O-(dimethylthiocarbamoyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (9), and was accompanied by 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (11). The 3-deoxy-3-iodo analog (14) of 11 underwent conversion into 10 by photolysis, and the deoxy sugar 10 was also prepared from 3,3'-dithiobis(1,2:5,6-di-O-isopropylidene-α-D--glucofuranose) (12) by the action of Raney nickel. Photolysis of the 2-dimethylthiocarbamate (16) of methyl 3,4-O-isopropylidene-β-L-arabinopyranoside (18) gave the 2-deoxy derivative (17), together with the parent alcohol 18, and the same pair of products was obtained by the action of tributylstannane on the 2-(methylthio)thiocarbonyl derivative (19) of 18, although the dimethylthiocarbamate 16 was unreactive toward tributylstannane.     

6-thio and -seleno-β-D-glucose esters of dimethylarsinous acid

Syntheses of 2-Se-(1,2,3,4-tetra-O-acetyl-β-D-glucopyranosyl)-3-N,N-dimethyl-selenopseudourea hydroiodide (3), 1,2,3,4-tetra-O-acetyl-6-S-dimethylarsino-6-thio-β-D-glucopyranose (4), 1,2,3,4-tetra-O-acetyl-6-Se-dimethylarsino-6-seleno-β-D-glucopyranose (7), 6-S-dimethylarsino-6-thio-β-D-glucopyranose (5), and 6-Se-dimethylarsino-6-seleno-β-D-glucopyranose (9) are described. Various spectral properties of the compounds are given. The relative rates of alkaline hydrolysis of 5 and 9 are compared.     

The synthesis and N.M.R. spectroscopy of derivatives of 6-amino-6-deoxy-D-galactose-6-15N

Derivatives of 6-amino-6-deoxy-D-galactose-6-¹⁵N have been synthesized by reaction of the 6-deoxy-6-iodo (1) or 6-O-p-tolylsulfonyl derivative of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose with potassium phthalimide-¹⁵N. The reaction of 1 also yielded an elimination product, 6-deoxy-1,2:3,4-di-O-isopropylidene-β-L-arabino-hex-5-enopyranose. The structures of the 6-amino-6-deoxy-D-galactose derivatives and their precursors were characterized by proton- and ¹³C-n.m.r. spectroscopy, with confirmation of the ¹³C assignments by selective proton decoupling. Selective broadening of the C-1, C-4, C-5, and C-6 resonances of 6-amino-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose by low concentrations of cupric ion was observed, and studied by computerized measurements of the ¹³C linewidths. The application of this broadening to ¹³C-spectral assignments of amino sugar derivatives is indicated.     

Analysis of sugar derivatives by chemical-ionization mass-spectrometry

D-Glucose diethyl dithioacetal (1), its penta-O-acetyl derivative (2), penta-O-acetyl-aldehydo-D-glucose (3), L-xylo-hexulose phenylosotriazole (4), 1,2:5,6-di-O-isopropylidene-D-mannitol (5), 1,2:4,5-di-O-isopropylidene-β-D-fructopyranose (6), 1,2-O-isopropylidene-α-D-glucofuranose (7) and its triacetate (8), 1,6-anhydro-β-D-galactopyranose (9) and its triacetate (10), D-glucopyranose (11), methyl β-D-glucopyranoside tetraacetate (12), 1-thio-β-D-glucopyranose pentaacetate (13), β-D-fructofuranose pentaacetate (14), and raffinose hendecaacetate (15) have been examined by chemical-ionization mass-spectrometry with both isobutane and ammonia as ionizing intermediates. Extreme simplicity characterizes these spectra, and, in most instances, molecular-weight data are available from intact, protonor NH₄⁺capture ions; the limited fragmentation that occurs corresponds in large measure to simple dehydration or substituent-cleavage processes, and is strongly dependent upon the groups present, so that considerable information about the substituent groups in the sugar molecule may be inferred.     

Isopropylidene acetals of 5-Thiopentopyranoses

Both 5-thio-D-ribose and 5-thio-D-xylose react with acetone and 2,2-dimethoxypropane, respectively, in the presence of acids to give 1,2:3,4-di-O-isopropylidene-5-thio-α-D-ribo- and -xylo-pyranoses (9 and 8); no furanoid products were detected. Partial hydrolysis of the xylo-diacetal 8 gave 1,2-O-isopropylidene-5-thio-α-D-xylopyranose, but a monoacetal could not be obtained from the ribo-diacetal 9. The methyl 5-thio-D-ribopyranosides (12) also react with acetone, giving only the 3,4-acetal from the α anomer 12a, and a separable mixture of 2,3- and 3,4-acetals from the β anomer 12b.     

The synthesis of racemic purpurosamine B

Starting from methyl 4,6-dichloro-4,6-dideoxy-α-D-galactopyranoside (1), D-chalcose (4,6-dideoxy-3-O-methyl-D-xcylo-hexopyranose) (5) was prepared by dechlorination with tributyltin hydride, selective benzoylation with benzoyl cyanide at O-2, methylation at O-3, and acid hydrolysis. D-Chalcose (5) was obtained as well by direct methylation of 1 with diazomethane at O-3, reduction with tin hydride, and hydrolysis. Chalcosyl bromide prepared from 5 was not very suitable for β-glycoside synthesis under Koenigs-Knorr conditions, and better results were obtained with 2- O-acetyl-4,6-dichloro-4,6-dideoxy-3-O-methyl-α-D-galactopyranosyl bromide, which gave β-glycosides with methanol, cyclohexanol, benzyl alcohol, 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose, and methyl 2,3-di-O-benzyl-6-deoxy-α-D-glucopyranoside. After dechlorination with tributyltin hydride, the corresponding β-glycosides of D-chalcose were obtained in good yield.     

4-deoxy-4-fluoro-1,2-O-isopropylidene-β-D-xylo-hexulopyranose

A 5-stage synthesis of the title compound (11), the first example of a secondary deoxyfluoroketose, is described. The synthesis comprised the following reaction sequence: D-fructose→1,2:4,5-di-O-isopropylidene-β-D-fructopyranose (4)→1,2:4,5-di-O-isopropylidene-3-O-tosyl-β-D-fructopyranose (3)→ 3,4-anhydro-1,2-O-isopropylidene-β-D-ribo-hexulopyranose (9)→4-deoxy-fluoro-1,2-O-isopropylidene-β-D-xylo-hexulopyranose (11). Fluoride displacement at C-4 in 9 was effected with tetrabutyl-ammonium fluoride in methyl cyanide. Similar treatment of either 3 or 1,2:4,5-di-O-isopropylidene-3-O-tosyl-β-D-ribo-hexulopyranose (5) failed to yield a fluoro derivative. Compound 5 was prepared by the sequence 4→1,2:4,5-di-O-isopropylidene-β-D-erythro-hexo-2,3-diulopyranose (6)→1,2:4,5-di-O-isopropylidene-β-D-ribo-hexulopyranose (7)→5.     

Dr. Horace S. Isbell

Addition of ethyl isocyanoacetate in strongly basic medium to the glycosuloses 1,2:5,6-di-O-isopropylidene-α-d-ribo-hexofuranos-3-ulose (1) and 1,2-O-isopropylidene-5-O-trityl-d-erythro-pentos-3-ulose (2) gave the unsaturated derivatives (E)- and (Z)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (3 and 4), and (E)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2-O-isopropylidene-5-O-trityl-α-d-ribofuranose (5). In weakly basic medium, ethyl isocyanoacetate and 1 gave 3-C-ethoxycarbonyl(formylamino)methyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (12) in good yield. The oxidation of 3 and 4 with osmium tetraoxide to 3-C-ethoxalyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (17), and its subsequent reduction to 3-C-(R)-1′,2′-dihydroxyethyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (18) and its (S) epimer (19) and to 3-C-(R)-ethoxycarbonyl(hydroxy)methyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (21) and its (S) epimer (22) are described. Hydride reductions of 12 yielded the corresponding 3-C-(1-formylamino-2-hydroxyethyl), 3-C-(2-hydroxy-1-methylaminoethyl), and 3-C-(R)-ethoxycarbonyl(methylamino)methyl derivatives (13, 14 and 16). Catalytic reduction of 3 and 4 yielded the 3-deoxy-3-C-(R)-ethoxycarbonyl-(formylamino)methyl derivative 6 and its 3-C-(S) epimer. Further reduction of 6 gave 3-deoxy-3-C-(R)-(1-formylamino-2-hydroxyethyl)-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (23) which was deformylated with hydrazine acetate to 3-C-(R)-(1-amino-2-hydroxyethyl)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (24). The configurations of the branched-chains in 16, 21, and 22 were determined by o.r.d.     

Synthesis of higher-carbon sugars via vinyltin derivatives of simple monosaccharides

6-O-Benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto-oct-7-ynopyranose reacted with tributyltin hydride to afford (Z-6-O-benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-8-(tributylstannyl)-l-glycero-α-d-galacto-oct-7-enopyranose, which was subsequently isomerized to the E-olefin 4. Replacement of the tributyltin moietey with lithium in 4 afforded the vinyl anion which reacted with 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-pentodialdo-1,4-furanose, furnishing 3-O-benzyl-6-C-[(E)-6-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto-heptopyranos-7-ylidene] -60-deoxy-1,2-O-isopropylidene-α-d-gluco- (6) and -β-l-ido-furanose (7) in yields of ∼70 or ∼87% (depending on the temperature of the reaction). The configurations of the new chiral centers in 6 and 7 were determined by their conversion into 3-O-benzyl-1,2-O-isopropylidene-α-d-gluco- and -β-l-ido-furanose, respectively. Oxidation of 6 and 7 gave the same enone, 3-O-benzyl-6-C-[(E)-6-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto- heoptopyranos-7-ylidene]-6-deoxy-1,2-O-isopropylidene-α-d-xylo-hexofuranos-5-ulose.     

Silica gel-catalyzed migration of acetyl groups from a sulfur to an oxygen atom

During the chromatographic separation of 3-S-acetyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose on silica gel, a migration of the acetyl group from S to O was observed to give 6-O-acetyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose, whereas 3-S-acetyl-6-O-benzoyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose gave 5-O-acetyl-6-O-benzoyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose. No acetyl migration was observed, however, in the case of 3-O-acetyl-1,2-O-isopropylidene-α-d-allofuranose.     

Sugar orthocarbonates

A simple procedure is described for preparing sugar orthocarbonates. It is based on treating the corresponding thionocarbonate in pyridine with cupric acetate and an alcohol, such as methanol, ethanol, or isopropyl alcohol. Treatment of 1,2:5,6-di-O-isopropylidene-D-mannitol 3,4-thionocarbonate with diols, such as 1,2-ethanediol, 1,2-propanediol, or 1,2:5,6-di-O-isopropylidene-D-mannitol, also gave orthocarbonates. Methyl thionocarbonate, S-methyl xanthate, and dithiobis(thioformate) derivatives of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose all gave the trimethyl orthocarbonate upon treatment with methanol in the presence of pyridine and cupric acetate. The structure of the orthocarbonates was proved by elemental analysis, n.m.r., and mass spectra, and by treatment with mild acid to form carbonates. Treatment of 1,2:5,6-di-O-isopropylidene-3-thio-D-altritol 3,4-thionocarbonate with methanol or ethanol gave the corresponding orthothiocarbonate, but on treatment with 1,2-ethanediol or with sodium ethoxide the 3,4-episulfide resulted.     

Acetonation of d-ribose and d-arabinose with alkyl isopropenyl ethers

d-Ribose (1) in N,N-dimethylformamide containing a trace of p-toluenesulfonic acid is acetonated under kinetic control by ethyl (or methyl) isopropenyl ether (2) to give mainly 3,4-O-isopropylidene-β-d-ribopyranose (3), together with lesser proportions of 2,3-O-isopropylidene-d-ribofuranose (4), its 5-(2-alkoxy-2-propyl) ether (5 or 5a), and 1,5:2,3-di-O-isopropylidene-β-d-ribofuranose (6). Similar treatment of d-arabinose (10) gives mostly 3,4-O-isopropylidene-β-d-arabinopyranose (11) together with a minor proportion of 1,2:3,4-di-O-isopropylidene-β-d-arabinopyranose (12). The strucutres of the monoacetals 3 and 11 were confirmed by an acetylation-deacetonation-acetylation sequence.     

Branched-chain glycosyl α-amino acids : Part II. Synthesis of 2-D- and 2-L-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)glycine. Analogs of the sugar moiety of the polyoxins

Stereospecific hydroxylation of 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-trans-and 3-C-cis-(methoxycarbonylmethylene)-α-D-ribo-hexofuranose (2 and 3, respectively), with potassium permanganate in pyridine afforded 3-C-[S- and R-hydroxy-(methoxycarbonyl)methyl]-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose, (6 and 7, respectively), in a combined yield, after chromatography, of 43%. Selective formation of monomethanesulfonates (9a and 10a) and p-toluenesulfonates (9b and 10b), followed by treatment with sodium azide and reduction of the azide, afforded the methyl 2-D-(and 2-L-)(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)-glycinates (12a and 13a, respectively). Basic hydrolysis of the latter compounds yielded 2-D- and 2-L-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)glycine (12b and 13b, respectively). The structures of the glycosyl amino acids were correlated with that of L-alanine by circular dichroism.     

Glycosyl α-amino acids : Part III. Synthesis of D- and L-2-(1,2:5,6-DI-O-isopropylidene-α-D-galactofuranos-3-YL)glycine

Stereospecific hydroxylation of (E)-3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-(methoxycarbonylmethylene)-α-D-xylo-hexofuranose (2) with potassium permanganate in pyridine afforded pure 3-C-[(R)-hydroxy(methoxycarbonyl)methyl]-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose (5) in 55% yield. Mesylation of the diol 5 in pyridine yielded the monomethanesulfonate 6 and, in addition, a small proportion of an unsaturated, exocyclic sulfonate 7. Treatment of 6 with sodium azide in N-N-dimethylformamide and reduction of the resultant α-azido ester 9 afforded methyl D- (and L-) 2-(1,2:5,6-di-O-isopropylidene-α-D-galactofuranos-3-yl)glycinate, (11a) and (10a), respectively. Basic hydrolysis of 11a and 10a yielded D- and L-2-(1,2:5,6-di-O-isopropylidene-α-D-galactofuranos-3-yl)glycine (11b) and (10b), respectively. The structures of the glycosyl α-amino acids were correlated with that of L-alanine by circular dichroism.     

Nucleosides LXXXIII. Synthetic studies on nucleoside antibiotics. 11. Synthesis of methyl 4-amino-3,4-dideoxy-β-D-ribo-hexopyranoside and -hexopyranosiduronic acid (derivatives related to the carbohydrate moiety of gougerotin)

Methyl 4-amino-3,4-dideoxy-β-D-ribo-hexopyranoside (17) and its uronic acid (19) were synthesized via a series of reactions starting from 1,2:5,6-di-O-isopropylidene-3-O-tosyl-α-D-glucofuranose. A method suitable for the large scale preparation of 3,4-dideoxy- 1,2:5,6-di-O-isopropylidene-α-D-erythro-hex-3-enofuranose(2) was devised.     

An approach to the synthesis of branched-chain amino sugars from c-methylene sugars

The reaction of 1,2:5,6-di-O-isopropylidene-3-C-methylene-α-D-ribo-hexofuranose (4) with mercuric azide in hot 50% aqueous tetrahydrofuran yielded, after reductive demercuration, 3-azido-3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methyl-α-D-glucofuranose (5). Partial, acid hydrolysis of5 afforded the diol7, which gave 3-azido-3-deoxy-1,2-O-isopropylidene-5,6-di-O-methanesulphonyl-3-C-methyl-α-D-glucofuranose (8) on sulphonylation. On hydrogenation over a platinum catalyst and N-acetylation, the dimethanesulphonate 8 furnished 3,6-acetylepimino-3,6-dideoxy-1,2-O-isopropylidene-5-O-methanesulphonyl-3-C-methyl-α-D-glucofuranose (9), which was also prepared by an analogous sequence of reactions on 3-azido-3-deoxy-1,2-O-isopropylidene-5-O-methanesulphonyl-3-C-methyl-6-O-toluene-p-sulphonyl-α-D-glucofuranose (13). The formation of the N-acetylepimine 9 establishes the D-gluco configuration for 5.1,2-O-Isopropylidene-3-C-methylene-α-D-ribo-hexofuranose (20) reacted with mercuric azide in aqueous tetrahydrofuran at ≈85° to give 3,6-anhydro-1,2-O-isopropylidene-3-C-methyl-α-D-glucofuranose (22) as a result of intramolecular participation by the C-6 hydroxyl group in the initial intermediate.