CD and NMR assignment of the anomeric configuration of 4-(5-deoxy-α,β-l-arabinofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs

Acid-catalyzed dehydrative cyclization of 5-deoxy-l-manno-pentitol-1-yl)-2-heptulose bisphenylhydrazone and subsequent reflux with copper sulfate gave an anomeric mixture of 4-(5-deoxy-α,β-l-arabinofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs. The mixture was separated by chromatography, and the anomeric compositions configurations of the components were determined by CD, NMR, mass spectroscopy, and acylation.     

Synthesis of C-glycopyranosylfuran derivatives by reaction of dialdehydes with cyanoacetamide

The reaction of diglycol- and thiodiglycol-aldehyde (1a,b) with cyanoacetamide yields cis-3,5-diacetoxy-4-carbamoyl-4-cyano-tetrahydropyran (2a) and -tetrahydrothiopyran (2b). When this reaction is applied to (2S)-2-(3-ethoxycarbonyl-2-methyl-5-furyl)-3,5-dihydroxy-1,4-dioxane (1c), (2S)-3,5-dihydroxy-2-(3-methoxycarbonyl-2-methyl-5-furyl)-1,4-dioxane (1d), and (2S,3R,5S)-2-(3-acetyl-2-methyl-5-furyl)-3,5-dihydroxy-1,4-dioxane (1e), 5-(3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-ethoxycarbonyl-2-methylfuran (2c), 5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-methoxycarbonyl-2-methylfuran (2e), and 3-acetyl-5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-2-methylfuran (2f), respectively, are formed with (4S,5S)-4-carbamoyl-4-cyano-2-(3-ethoxycarbonyl-2-methyl-5-furyl)-5-hydroxy-5,6-dihydropyran (3a) and (4S,5S)-4-carbamoyl-4-cyano-5-hydroxy-2-(3-methoxycarbonyl-2-methyl-5-furyl)-5,6-dihydropyran (3b) as minor products. The dehydration of 2a,b, 5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-ethoxycarbonyl-2-methylfuran (2d), 2e, and 2f yields cis-3,5-diacetoxy-4,4-dicyano-tetrahydropyran and -tetrahydrothiopyran (2l,m), and the 5-(2,4-di-O-acetyl-3,3-dicyano-3-deoxy-β-d-erythro-pentopyranosyl) derivatives (2n–p) of 3-ethoxycarbonyl-2-methylfuran, 3-methoxycarbonyl-2-methylfuran, and 3-acetyl-2-methylfuran, respectively.     

Reactions of the 3-oxime 2-phenylhydrazone and mixed bishydrazones of dehydro-L-ascorbic acid: Conversion into substituted triazoles and pyrazolinediones

L-threo-2,3-Hexodiulosono-1,4-lactone 2-phenylhydrazone(1) reacted with hydroxylamine to give the 3-oxime 2-phenylhydrazone(2). On boiling with acetic anhydride,2 was dehydrated to 4-[L-threo-2,3-diacetoxy-(1-hydroxypropyl)]-2-phenyl-1,2,3-triazole-5-car?ylic acid lactone(3), which was converted into 2-phenyl-4-(L-threo-1,2,3-trihydroxypropyl)-1,2,3-triazole-5-car?amide(4) with liquid ammonia. The structure of compound4 was confirmed by acetylation to 2-phenyl-4-(L-threo-1,2,3-triacetoxypropyl)-1,2,3-triazole-5-car?amide(5), and by periodate oxidation followed by reduction, to give 4-(hydroxymethyl)-2-phenyl-1,2,3-triazole-5-car?amide(6). Treatment of compound1 with aryl- or aroyl-hydrazines afforded mixed bishydrazones(7–14), which were acetylated to15–21, and treated with hydrazine to give pyrazolinediones22 and23     

Homo-C-nucleoside analogs III. Studies on the base-catalyzed dehydrative cyclization of 4-(d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole

Treatment of 4-(d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole with one molar equivalent of 2,4,6-triisopropylbenzenesulfonyl chloride (TIBSCl) in pyridine solution afforded the homo-C-nucleoside analog; 4-(2,5-anhydro-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole in 54% yield and 4-(α-d-arabinopyranosyl)-2-phenyl-2H1,2,3-triazole analog in 3% yield. The 4-(5-O-triisopropylbenzenesulfonyl)-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole analog was isolated as an intermediate and identified as its tetra-O-acetyl derivative. The 4-(5-chloro-5-deoxy-d-manno-pentitol-1-yl)-2-phenyl-2H-1,2,3-triazole analog was isolated as a byproduct. The structure and anomeric configuration of the products were determined by acylation, NMR spectroscopy, and mass spectrometry.     

Studies on anhydro-osazones. Structure and anomeric configuration of the 3,6-anhydro-osazone derivatives obtained from D-galacto-2-heptulose phenylosazone

Dehydration of D-galacto-2-heptulose phenylosazone with methanolic sulfuric acid afforded two 3,6-anhydro-osazone derivatives (2 and 3). Compound 2 was obtained as the preponderant isomer, without inversion at C-1 (C-3 of the starting osazone), and 3 was obtained with inversion. The anomeric configurations of 2 and 3 were determined by n.m.r. spectroscopy. Refluxing of 2 and 3 with copper sulfate afforded two C-nucleoside analogs, namely, 4-β- and 4-α- D-lyxofuranosyl-2-phenyl-1,2,3-triazole, 4 and 5, respectively. The anomeric configurations of 4 and 5 were determined by n.m.r and c.d. spectroscopy. Acetylation of 4 and 5 afforded the tri-O-acetyl derivatives. The mass spectra of these compounds were discussed.     

Synthesis and biological activity of O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses

Benzoylation of benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-α-d-glucopyranoside, benzyl 2-deoxy-2-(dl-3-hydroxytetradecanoylamino)-4,6-O-isopropylidene-α-d-glucopyranoside, and benzyl 2-deoxy-4,6-O-isopropylidene-2-octadecanoylamino-β-d-glucopyranoside, with subsequent hydrolysis of the 4,6-O-isopropylidene group, gave the corresponding 3-O-benzoyl derivatives (4, 5, and 7). Hydrogenation of benzyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-glucopyranoside, followed by chlorination, gave a product that was treated with mercuric actate to yield 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucopyranose (11). Treatment of 11 with ferric chloride afforded the oxazoline derivative, which was condensed with 4, 5, and 7 to give the (1→6)-β-linked disaccharide derivatives 13, 15, and 17. Hydrolysis of the methyl ester group in the compounds derived from 13, 15, and 17 by 4-O-acetylation gave the corresponding free acids, which were coupled with l-alanyl-d-isoglutamine benzyl ester, to yield the dipeptide derivatives 19–21 in excellent yields. Hydrolysis of 19–21, followed by hydrogenation, gave the respective O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses in good yields. The immunoadjuvant activity of these compounds was examined in guinea-pigs.     

Sugars containing a carbon-phosphorus bond : Part V. 5-deoxy-5-(ethylphosphinyl)-D-ribopyranose

The Michaelis-Arbuzov reaction of methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-β-D-ribofuranoside (4) with diethyl ethylphosphonite gave methyl 5-deoxy-5-(ethoxyethylphosphinyl)-2,3-O-isopropylidene-β-D-ribofuranoside (5) which, on treatment with sodium dihydrobis(2-methoxyethoxy)aluminate, afforded methyl-5-deoxy-5-(ethylphosphinyl)-2,3-O-isopropylidene-β-D-ribofuranoside (9). Hydrolysis of 9 with hydrochloric acid yielded a mixture of the anomeric 5-deoxy-5-(ethylphosphinyl)-D-ribopyranoses (10). The hygroscopic, syrupy mixture 10 was converted into a syrup consisting of the two 1,2,3,4-tetra-O-acetyl-5-deoxy-5-(ethylphosphinyl)-D-ribopyranoses (11).     

The synthesis of 5-O-(2-acetamido-2-deoxy-α-D-glucopyranosyl)-β-D-glucofuranose

Condensation of dimeric 3,4,6-tri-O-acetyl-2-deoxy-2-nitroso-α-D-glucopyranosyl chloride (1) with 1,2-O-isopropylidene-α-D-glucofuranurono-6,3-lactone (2) gave 1,2-O-isopropylidene-5-O-(3,4,6-tri-O-acetyl-2-deoxy-2-hydroxyimino-α-D-arabino-hexopyranosyl)-α-D-glucofuranurono-6,3-lactone (3). Benzoylation of the hydroxyimino group with benzoyl cyanide in acetonitrile gave 1,2-O-isopropylidene-5-O-(3,4,6-tri-O-acetyl-2-benzoyloxyimino-2-deoxy-α-D-arabino-hexopyranosyl)-α-D-glucofuranurono-6,3-lactone (4). Compound 4 was reduced with borane in tetrahydrofuran, yielding 5-O-(2-amino-2-deoxy-α-D-glucopyranosyl)-1,2-O-isopropylidene-α-D-glucofuranose (5), which was isolated as the crystalline N-acetyl derivative (6). After removal of the isopropylidene acetal, the pure, crystalline title compound (10) was obtained.     

Synthesis of 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-D-mannose,and its interaction with D-mannose-specific lectins

Condensation of 3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal with 2-methyl-(3,4,6-tri-O-acetyl- 1,2-dideoxy-α-D-glucopyrano)-[2′, 1′:4,5]-2-oxazoline in the presence of a catalytic amount of p-toluenesulfonic acid afforded crystalline 2-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal (3) in 25% yield. Catalytic deacetylation of 3 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave 2-O-(2-acetamido-2-deoxy-α-D-glucopyranosyl)-D-mannose (4). Treatment of 3 with boiling 0.5% methanolic hydrogen chloride under reflux gave methyl 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannopyranoside (5) and methyl 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannofuranoside (6). The inhibitory activities of 4, 5, and 6 against the hemagglutinating and mitogenic activities of Lens culinaris and Pisum sativum lectins and concanavalin A were assayed. From the results of these hapten inhibition studies, subtle differences of specificity between these D-mannose-specific lectins were confirmed.     

Synthesis of prumycin and related compounds

Prumycin (1) and related compounds have been synthesized from benzyl 2-(benzyloxycarbonyl)amino-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside (4). Benzoylation of 4, followed by deisopropylidenation, gave benzyl 3-O-benzoyl-2-(benzyloxycarbonyl)amino-2-deoxy-β-d-glucofuranoside (6), which was converted, via oxidative cleavage at C-5–C-6 and subsequent reduction, into the related benzyl β-d-xylofuranoside derivative (7). Benzylation of 3-O-benzoyl-2-(benzyloxycarbonyl)-amino-2-deoxy-d-xylopyranose (8), derived from 7 by hydrolysis, afforded the corresponding derivatives (9, 11) of β- and α-d-xylopyranoside, and compound 7 as a minor product. Treatment of benzyl 3-O-benzoyl-2-(benzyloxycarbonyl)amino-2-deoxy-4-O-mesyl-β-d-xylopyranoside 10, formed by mesylation of 9, with sodium azide in N,N-dimethylformamide gave benzyl 4-azido-3-O-benzoyl-2-(benzyloxy-carbonyl)amino-2,4-dideoxy-α-l-arabinopyranoside (13), which was debenzoylated to compound 14. Selective reduction of the azide group in 14, and condensation of the 4-amine with N-[N-(benzyloxycarbonyl)-d-alaninoyloxy]succinimide, gave the corresponding derivative (15) of 1. Reductive removal of the protecting groups of 15 afforded 1. Prumycin analogs were also synthesized from compound 14. Evidence in support of the structures assigned to the new derivatives is presented.     

Stereospecific synthesis of chiral benzylic centers from D-erythro-pentulose derivatives

Stereospecific, Grignard addition reactions are described that afford C-phenyl branched-chain pentitols having either the D-arabino(2) or D-ribo(19) stereochemistry, according to the mode of substitution of the starting 2-pentulose. The reaction of 3,5-O-benzylidene-1-deoxy-D-erythro-2-pentulose (1) with phenyl-magnesium bromide led stereospecifically to 3,5-O-benzylidene-1-deoxy-2-C-phenyl-D-arabinitol (2), the configuration of which was established by a nuclear Overhauser experiment with its 2,4:3,5-dibenzylidene acetal (3). Acid hydrolysis of 2 led to the novel, crystalline 1-deoxy-2-C-phenyl-D-arabinitol (4), further characterized as its triacetate 5. In attempts to mask certain hydroxyl groups of 2 selectively, the 2,4-O-isopropylidene (6) and 2,4-O-carbonyl (7) derivatives, the 4-acetate 8, the 4-(trimethylsilyl) and 4-(tert-butyldimethylsilyl) ethers (10 and 17), and the corresponding 2-phenylcarbamates 9 (from 8) and 11 (from 10) were prepared. Catalytic hydrogenolysis of the carbamates 9 and 11 resulted in deoxygenation of the benzylic center with inversion of configuration to give 2(S)-3,5-O-benzylidene-1,2-dideoxy-2-C-phenyl-D-erythro-pentitol (12; from 11) and its 4-O-acetyl analog 13 (from 9). Benzylation of the trimethylsilyl ether 10 afforded 2-O-benzyl-3,5-O -benzylidene-1-deoxy-2-C-phenyl-4-O-(trimethylsilyl)-D-arabinitol (15), together with the corresponding 2,4-dibenzyl ether 14. Acid hydrolysis of 15 yielded the crystalline, branched-chain, benzyl ether 16. The tert-butyldimethylsilyl ether of 1 reacted with phenylmagnesium bromide to give, exclusively, the C-phenyl branched-chain pentitol (19) having the D-ribo stereochemistry.     

The stereochemistry of palladium- and platinum-catalyzed hydrogenations of nitro sugar epoxides

The catalytic hydrogenation of carbohydrate α-nitroepoxides with palladium and platinum was investigated with regard to regiospecificity and stereochemistry of ring opening, and the fate of the nitro group. 5,6-Anhydro-1,2-O-isopropylidene- 6-C-nitro-α-D-glucofuranose gave 6-amino-6-deoxy-1,2-O-isopropylidene-α-D-gluco-furanose under platinum catalysis. The methyl 2,3-anhydro-4,6-O-benzylidene-3-C- nitrohexopyranosides having the β-D-gulo (4), ?-D-allo (9), α-D-manno (13), and β-D-manno (18) configurations underwent facile, hydrogenolytic ring-opening in the presence of palladium, to give, regardless of the orientation of the oxirane ring, methyl 4,6-O-benzylidene-3-deoxy-3-C-nitro-D-hexopyranosides having an equatorial nitro group (5, 10, 14, and 19, respectively). In addition, 3-deoxy-3-oximino derivatives arose in various proportions, and two of these (from 9, and from 18) were isolated crystalline. It was shown that the oximes did not result from over-hydrogenation of the 3-deoxy-3-C-nitro glycosides produced, and it is suggested that they originated from intermediary nitronic acids. By catalysis with platinum, the oxirane rings in 4, 9, 13, and 18 were opened in the same regiospecific sense as with palladium, but notable differences were observed otherwise. Compound 4 gave the amino analog of 5, whereas 9 retained the nitro group and gave the 4,6-O-(cyclohexylmethylene) analog of 10. The α-D-manno epoxide 13 reacted with concomitant debenzylidenation, to yield methyl 3-amino-3-deoxy-α-D-altropyranoside hydrochloride, whereas the β-D-manno epoxide 18 gave the corresponding, debenzylidenated amino β-D-altroside together with the 4,6-O-(cyclohexylmethylene)-3-nitro- and -3-amino-β-D-mannosides. The results are compared with literature reports on the stereochemistry of hydrogenolysis of oxiranes, and mechanisms that may operate for the nitro derivatives are discussed.     

Synthesis of novel 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitrile derivatives as antimicrobial and antioxidant agents

As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2a–i), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5a–i), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6a–i) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7a–i). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe³⁺) reducing antioxidant power (FRAP) and metal chelating activity.     

The synthesis of oligosaccharide-asparagine compounds. V. O- -D-mannopyranosyl-(1 leads to 6)-O-(2-acetamido-2-deoxy- -D-glucopyranosyl)-(1 leads to 4)-2-acetamido-N-(L-aspart-4-oyl)-2-deoxy- -D-glucopyranosylamine

O-α-d-Mannopyranosyl-(1→6)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→4)-2-acetamido-N-(l-aspart-4-oyl)-2-deoxy-β-d-glucopyranosylamine (12), used in the synthesis of glycopeptides and as a reference compound in the structure elucidation of glycoproteins, was synthesized via condensation of 2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl bromide with 2-acetamido-4-O-(2-acetamido-3-O-acetyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-acetyl-2-deoxy-β-d-glucopyranosyl azide (5) to give the intermediate, trisaccharide azide 7. [Compound 5 was obtained from the known 2-acetamido-4-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-acetyl-2-deoxy-β-d-glucopyranosyl azide by de-O-acetylation, condensation with benzaldehyde, acetylation, and removal of the benzylidene group.] The trisaccharide azide 6 was then acetylated, and the acetate reduced in the presence of Adams' catalyst. The resulting amine was condensed with 1-benzyl N-(benzyloxycarbonyl)-l-aspartate, and the O-acetyl, N-(benzyloxycarbonyl), and benzyl protective groups were removed, to give the title compound.     

The relationship of molecular weight, and sulfate content and distribution to anticoagulant activity of heparin preparations

The crystalline intermediate 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranosyl azide (5), obtained by condensation of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl bromide with either 2-acetamido-3,4-di-O-acetyl-2-deoxy-β-D-glucopyranosyl azide or its 6-O-triphenylmethyl derivative, was reduced in the presence of Adams' catalyst to give a disaccharide amine. Condensation with 1-benzyl N-(benzyloxycarbonyl)-L-aspartate afforded crystalline 2-acetamido-6-O-(2-acetamido-3,4 6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4-di-O-acetyl-1-N-[1-benzyl N-(benzyloxycarbonyl)-L-aspart-4-oyl]-2-deoxy-β-D-glucopyranosylamine (9). Catalytic hydrogenation in the presence of palladium-on-charcoal was followed by saponification to give 2-acetamido-6-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-1-N-(L-aspart-4-oyl)-2-deoxy-β-D-glucopyranosylamine (11) in crystalline form. From the mother liquors of the reduction of 5, a further crystalline product was isolated, to which was assigned a bisglycosylamine structure (12).     

Synthesis of novel 1,2,3-triazole tagged pyrazolo[3,4-b]pyridine derivatives and their cytotoxic activity

A series of novel 1,2,3-triazole tagged pyrazolo[3,4-b]pyridine derivatives 3 and 4 were prepared respectively starting from 6-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 1 via selective N-propargylation, followed by reaction with diverse substituted alkyl/perfluoroalkyl/aryl/aryl amide azides under Sharpless conditions. All the synthesized compounds 3 and 4 were screened for cytotoxic activity against four human cancer cell lines such as U937, THP-1, HL60 and B16-F10. Compounds 3e, 4g, 4i and 4j which showed promising activity have been identified.     

5-thio-l-rhamnose

Two routes for the synthesis of methyl 5-S-acetyl-6-deoxy-2,3-O-isopropylidene-5-thio-l-mannofuranoside (8) have been examined. Reaction of l-rhamnose with methanol in the presence of the cation-exchange resin gives methyl 6-deoxy-α-l-mannofuranoside (2), which on conventional acetonation yields methyl 6-deoxy-2,3-O- isopropylidene-α-l-mannofuranosides (3). Compounds 3 is also obtained by acetonation of l-rhamnose followed by treatment with a mixture of methanol, acetonation, Amberlite IR-120(H⁺) resin. Chlorination of 3 with triphenylphosphine-carbon tetrachloride gives methyl 5-chloro-5,6-dideoxy-2,3-O-isopropylidene-β-d-gulofuranoside (7), which reacts with potassium thioacetate to give 8. Alternatively, 3 is iodized with ruthenium tetraoxide to methyl 6-deoxy-2,3-O-isopropylidene-α-l-lyxo-hexofuranosid-5-ulose (9), which reduced by sodium borohydride mainly to methyl 6-deoxy-2,3-O-isopropylidene-β-d-gulofuranoside (10). The O-tosyl derivative of 10 reacts with potassium thioacetate to produced 8. Hydrolysis of 8 with 90% aqueous triflouroacetic acid, followed by acetolysis with a solution of acetic acid, acetic anhydride, and sulfuric acids gives an anomeric mixture of 1,2,3,4,-tetra-O-acetyl-6-deoxy-5-thio-l-mannopyranoses (12), together with a small proportion of 1,2,3,-tri-O-acetyl-5-S-acetyl-6-deoxy-5-thio-β-l-mannofuranose (13). Deacetylation of 12 or 13 gives 5-thio-l-rhamnose (6), from which crystalline 1,2,3,4-tetra-O-(p-nitrobenzoyl)-5-thio-β-l-rhamnopyranose (14) is obtained.     

Fluorinated carbohydrates : Part XIII. 2-deoxy-2-fluoro-D-galactose

Reaction of trifluoro(fluoroxy)methane at ca. −80° with 3,4,6-tri-O-acetyl-D-galactal affords trifluoromethyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-galactopyranoside (2, 39%), 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-galactopyranosyl fluoride (3, 37%), trifluoromethyl 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-α-D-talopyranoside (4, 3%), and 3,4,6-tri-O-acetyl-2-deoxy-2-fluor-α-D-talopyranosyl fluoride (5, 2%). The structures of compounds 2–5 have been established by n.m.r. spectroscopy. Acid hydrolysis of 2 or 3 allords 2-deoxy-2-fluoro-D-galactose.     

Synthesis of 2,4-diacetamido-2,4,6-trideoxy-L-altrose, -L-idose, and -L-talose from benzyl 6-deoxy-3,4-O-isopropylidene-beta-L-galactopyranoside

Acetylation of benzyl 6-deoxy-3,4O-isopropylidene-β-L-galactopyranoside gave benzyl 2-O-acetyl-6-deoxy-3,4-O-isopropylidene-β-L-galactopyranoside (1). Removal of the isopropylidene group afforded benzyl 2-O-acetyl-6-deoxy-β-L-galactopyranoside (2), which was converted into benzyl 2-O-acetyl-6-deoxy-3,4-di-O-(methyl-sulfonyl)-β-L-galactopyranoside (3). Benzyl 2,3-anhydro-6-deoxy-4-O-(methyl-sulfonyl)-β-L-gulopyranoside (4) was obtained from 3 by treatment with alkali. Reaction of 4 with sodium azide in N,N-dimethylformamide gave a mixture of two isomeric benzyl 2,4-diazido-2,4,6-trideoxy hexoses, the syrupy diazido derivative 5 and the crystalline benzyl 2,4-diazido-2,4,6-trideoxy-β-L-idopyranoside (6). Acetylation of 6 afforded a compound whose n.m.r. spectrum was completely first order and in agreement with the structure of benzyl 3-O-acetyl-2,4-diazido-2,4,6-trideoxy-β-L-idopyranoside (7). Lithium aluminium hydride reduction of 5, followed by acetylation, afforded a crystalline product (8), shown by n.m.r. spectroscopy to be benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β-L-altropyranoside. Similar treatment of the diazido derivative 6 afforded benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β-L-idopyranoside (9). Compounds 8 and 9 could also be obtained from 4 by treatment of the crude diazido mixture with lithium aluminium hydride, with subsequent N-acetylation. The syrupy benzyl 2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranoside (10) and the crystalline benzyl 2,4-diacetamido-2,4,6-trideoxy-β-L-idopyranoside (11) thus obtained were then O-acetylated to give 8 and 9 respectively. Benzyl 2,4-diacetamido-2,4,6-trideoxy-β-L-talopyranoside (15) was obtained from 11 by treatment with methanesulfonyl chloride and subsequent solvolysis. Compound 15 was O-acetylated to yield benzyl 2,4-diacetamido-3-O-acetyl-2,4,6-trideoxy-β-L-talopyranoside (16). the n.m.r. spectrum of which was in full agreement with the assigned structure. The mass spectra of compounds 8–11, 15, and 16 were also in agreement with their proposed structures. Removal of the benzyl groups from 10, 11 and 15 afforded the corresponding 2,4-diacetamido-2,4,6-trideoxyhexoses 12, 13, and 17, having the L-altro, L-ido, and L-talo configurations, respectively.     

Enamine and pyrrole formation from 2-amino-2-deoxy-D-glucose and dimethyl acetylenedicarboxylate

Addition of 2-amino-2-deoxy-β-D-glucopyranose to dimethyl acetylenedicarboxylate afforded an almost quantitative yield of amorphous 2-deoxy-2-(1,2-dimethoxycarbonylvinyl)amino-D-glucose (5). Acetylation of this adduct gave crystalline 1,3,4,6-tetra-O-acetyl-2-deoxy-2-[(Z)-1,2-dimethoxycarbonylvinyl]amino-α-D-glucopyranose (6a); the corresponding β-D anomer (6b) was obtained by addition of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-Dglucopyranose to dimethyl acetylenedicarboxylate. O-Deacetylation of tetra-acetate 6a with barium methoxide in methanol occurred selectively at C-1, yielding enamine 6c derived from 3,4,6-tri-O-acetyl-2-amino-2-deoxy-α-D-glucopyranose. Conversion of the crude adduct 5 into 3-methoxycarbonyl-5-(D-arabino-tetrahydroxybutyl)-2-pyrrolecarboxylic acid (7) took place by heating in water or in slightly basic media in yields up to 83%. Acetylation of 7 gave the tricyclic derivative 8, and its periodate oxidation afforded 5-formyl-3-methoxycarbonyl-2-pyrrolecarboxylic acid (9). Oxidation of 9 with alkaline silver oxide yielded 3-methoxy-carbonyl-2,5-pyrroledicarboxylic acid (10).