Sugar Acetylenes Research Articles

Synthesis of C-substituted triazoles, isoxazoles, and pyrazoles by 1,3-dipolar cycloaddition to acetylenic sugars

Addition of phenyl azide to 3,5-di- O-acetyl-6,7-dideoxy-1,2- O-isopropylidene-β- l- idio-hept-6-ynofuranose ( 1) and subsequent saponification gave a 4-substituted 1-phenyl-1,2,3-triazole derivative ( 3) whose optical rotatory dispersion (o.r.d.) curve was positive. The α- d- gluco analog ( 5) of 1 similarly gave the 5-epimer ( 7) of 3; its o.r.d. curve was negative. Both 3 and 7 were degraded to the known 1-phenyl-1,2,3-triazole-4-carboxaldehyde. Similarly, addition of 2,4,6-trimethylbenzonitrile N-oxide to 1 or 5 gave the corresponding, crystalline 3-mesitylisoxazoles as single products; 13C-n.m.r. spectroscopy was used to establish the orientation of addition. Related 3-mesitylisoxazoles ( 11 and 13) were obtained from 1,2:3,4-di- O-isopropylidene- d- glycero-α- d-galacto -oct-7-ynopyranose ( 10) and its l- glycero 6-epimer ( 12), respectively; 11 showed the expected, large levorotation, and the 6-epimer 13 was also levorotatory. Benzonitrile ( N-phenyl)imine, prepared in situ from 1-(α-chlorobenzylidene)-2-phenylhydrazine and base, did not react with 10 (or its 6-epimer 12), but did react with the 6-keto analog to give a 5-substituted 1,3-diphenyl-1,2-diazole.

ChemInform Abstract: ACETYLENIC SUGARS‐ SYNTHESIS OF 3‐O‐BENZOYL‐5,6‐DIDEOXY‐1,2‐O‐ISOPROPYLIDENE‐α‐D‐RIBO‐HEX‐5‐YNOFURANOSE

Chemischer InformationsdienstVolume 9, Issue 30 Natural Products ChemInform Abstract: ACETYLENIC SUGARS- SYNTHESIS OF 3-O-BENZOYL-5,6-DIDEOXY-1,2-O-ISOPROPYLIDENE-α-D-RIBO-HEX-5-YNOFURANOSE V. K. SRIVASTAVA, V. K. SRIVASTAVASearch for more papers by this author V. K. SRIVASTAVA, V. K. SRIVASTAVASearch for more papers by this author First published: July 25, 1978 https://doi.org/10.1002/chin.197830345AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume9, Issue30July 25, 1978 RelatedInformation

Synthesis of acetylenic sugars and uronic acids via two-carbon chain extension of d-ribose

Treatment of methyl β- d-ribofuranoside with acetone gave methyl 2,3- O-isopropylidene-β- d-ribofuranoside ( 1, 90%), whereas methyl α- d-ribofuranoside gave a mixture (30%) of 1 and methyl 2,3- O-isopropylidene-α- d-ribofuranoside ( 1a). On oxidation, 1 gave methyl 2,3- O-isopropylidene-β- d- ribo-pentodialdo-1,4-furanoside ( 2), whereas no similar product was obtained on oxidation of 1a. Ethynylmagnesium bromide reacted with 2 in dry tetrahydrofuran to give a 1:1 mixture (95%) of methyl 6,7-dideoxy-2,3- O-isopropylidene-β- d- allo- ( 3) and -α- l- talo-hept-6-ynofuranoside ( 4). Ozonolysis of 3 and 4 in dichloromethane gave the corresponding d- allo- and l- talo-uronic acids, characterized as their methyl esters ( 5 and 6) and 5- O-formyl methyl esters ( 5a and 6a). Ozonolysis in methanol gave a mixture of the free uronic acid and the methyl ester, and only a small proportion of the 5- O-formyl methyl ester. Malonic acid reacted with 2 to give methyl 5,6-dideoxy-2,3- O-isopropylidene-β- d- ribo- trans-hept-5-enofuranosiduronic acid ( 7).

Nouveaux types de sucres acétyléniques. Communication préliminaire

Novel types of acetylenic sugarsThe coupling, following Cadiot's procedure, of a 6‐bromo‐5,6‐dideoxy‐1,2‐O‐isopropylidène‐3‐O‐methyl‐α‐D‐xylo‐hex‐5‐yno‐1, 4‐furanose (1) with phenylacetylene, 2‐propyn‐1‐ol or terminal acetylenic sugars gave with excellent yields the expected diynes (an enediyne when the terminal acetylene was the 3,5, 6‐trideoxy‐1,2‐O‐isopropylidene‐α‐D‐glycero‐hex‐3‐en‐5‐yno‐1,4‐furanose 7). The chloro analogue 8 of 1 on treatment with lithium thiophenate gave the corresponding phenylthio‐acetylenic sugar 9. An acetylene was also formed by reacting the gem‐difluoro‐olefinic sugar 10 with butyllithium whereas the same olefinic sugar and its 3‐O‐benzyl analogue 11 gave only a gem‐fluoro‐arylthio‐olefinic sugar (13–15) as a mixture of the Z and E isomers (Z/E > 4) when treated with the conjugate base of an arylmercaptan.

Steric course of triazole formation from acetylenic sugars and phenyl azide

Condensation of the acetylenic sugar 1,2-dideoxy-4,5:6,7-di- O-isopropylidene- d- gluco-hept-1-ynitol ( 1) with phenyl azide gave mainly the 1-phenyl-1,2,3-triazole derivative ( 5) having the sugar chain at C-4, together with a minor proportion of the 5-substituted analogue ( 6). The d- manno analogue ( 2) of 1 reacted similarly, to give the corresponding 4-substituted ( 13) and 5-substituted ( 14) 1-phenyl-1,2,3-triazoles. Structures of the products were established by degrading 5 and 13 to 1-phenyl-1,2,3-triazole-4-carboxaldehyde ( 11), and 6 and 14 to 1-phenyl-1,2,3-triazole-5-carboxaldehyde ( 12). The optical rotatory behavior of the derivatives having an unsubstituted sugar chain attached to the triazole ring is in accord with the Generalized Heterocycle Rule, but the rule does not hold for some of the derivatives having substituents on the sugar chain.

Preparation of acetylenic sugar derivatives by way of 2-( N-nitroso)acetamido sugars

N-Nitrosation with dinitrogen tetraoxide was used to convert 2-acetamido-1,3,4,6-tetra- O-acetyl-2-deoxy-α- D-glucopyranose ( 1) and 2-acetamido-1,3,4,6-tetra- O-acetyl-2-deoxy-β- D-galactopyranose ( 4) in high yield into the N-nitroso derivatives 2 and 5, respectively. Similarly, 3-acetamido-1,2,4,6-tetra- O-acetyl-3-deoxy-β- D-glucopyranose ( 12) and methyl 2-acetamido-3,4,5,6-tetra- O-acetyl-2-deoxy- D-gluconate ( 15) gave their respective, crystalline N-nitroso derivatives 13 and 16. Various other 2-acetamido sugar derivatives were likewise nitrosated. In ethereal solution, compounds 2 and 16 reacted with potassium hydroxide in isopropyl alcohol to give the C 5 acetylene, 1,2-dideoxy- D- erythro-pent-1-ynitol, isolated as the known triacetate 3. By the same procedure, the galacto derivative 5 was converted in high yield into the 3-epimeric C 5 acetylene, 1,2-dideoxy- D- threo-pent-1-ynitol, isolated as its triacetate 6 and characterized by conversion into the known, crystalline 1,2-dideoxy-3- O-(3,5-dinitrobenzoyl)-4,5- O-isopropylidene- D- threo-pent-1-ynitol ( 7).

Conversion of a 2-( N-nitroso)acetamido hexose into a five-carbon, acetylenic sugar derivative

Dinitrogen tetraoxide was used to convert 2-acetamido-1,3,4,6-tetra- O-acetyl-2-deoxy-β- D-glucopyranose ( 1) in high yield into the syrupy N-nitroso derivative 2, and benzyl 2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β- D-glucopyranose ( 6) into the crystalline N-nitroso analog 7. The N-nitroso derivative 2 in acetonitrile underwent photolysis by pyrex-filtered, u.v. light to regenerate the starting acetamide 1 in high yield; spontaneous decomposition of 2 afforded β- D-glucopyranose pentaacetate ( 3) and other products. In ethereal solution, compound 2 reacted with potassium hydroxide in isopropyl alcohol with loss of the 2-substituent and C-1, to give a C 5 acetylene, 1,2-dideoxy- D- erythro-pent-1-ynitol, isolated in high yield as its triacetate 4 and characterized by conversion into the known, crystalline 1,2-dideoxy-3- O-(3,5- dinitrobenzoyl)-4,5- O-isopropylidene- D- erythro-pent-1-ynitol ( 5).

Utilisation d'ylides du phosphore en chimie des sucres. XX. Synthèse de sucres acétyléniques et réarrangment d'intermédiaires carbénoïdes. Communication préliminaire

AbstractTwo novel methods for the synthesis of terminal acetylenic sugars, both involving a chain extension by one carbon unit, are described. In the first procedure, an aldehydo‐sugar is treated with dibromomethylenetriphenyl‐phosphorane, then with n‐butyllithium and finally with water. The second method involves an one‐step reaction between an aldehydo‐sugar and dimethyl diazomethylphosphonate. The acetylenic sugars obtained are valuable synthetic intermediates for the preparation of heterocyclic C‐nucleosides by 1,3‐dipolar cycloaddition reactions and some examples of syntheses of this type are described. Treatment of keto‐sugars with dimethyl diazomethylphosphonate led to an intermediate carbenoid species which reacted by insertion into a CH bond in one case and underwent nucleophilic attack by a methoxy group in a second case.

Utilisation d'ylides du phosphore en chimie des sucres. XVIII Synthèse de furannoses à insaturation conjuguée. Communication préliminaire

AbstractSeveral sugars with conjugated unsaturation (dienes or α, β‐unsaturated carbonyl compounds) have been synthesised by use of Wittig reactions. Keto‐sugars bearing a carbonyl group α to a furanose ring are prone to undergo an elimination leading to conjugated unsaturated systems. This constitutes a novel kind of side‐reaction in the application of Wittig reactions to carbonyl sugars. The synthesis of a new kind of acetylenic sugar is also described.

Synthesis of triazole derivatives of sugars by 1,3-dipolar cycloaddition from acetylenic and azido precursors

1,2,3-Triazoles having sugar chains at C-4, and others having the chain at N-1, were prepared. Condensation of 3- O-acetyl-4,5- O-isopropylidene-1-pentyne- D- threo-3,4,5-triol ( 1) with phenyl azide, followed by removal of substituents, gave 1-phenyl-4-( D- threo-trihydroxypropyl)-1,2,3-triazole ( 2), whose structure was proved by oxidation to known derivatives of 1-phenyl-1,2,3-triazole. The 1-benzyl analog ( 4) of 2 was prepared similarly. The 4- C-substituted 1,2,3-triazole 12 was obtained in the same way from the acetylenic sugar derivative 11. By condensing phenylacetylene with the sugar azides 13 (primary azide), 15 (secondary azide), and 17 (glycosyl azide), the 1-substituted 4-phenyl-1,2,3-triazoles 14, 16, and 18, respectively, were obtained. The 4-substituted 1-phenyl-1,2,3-triazoles and 1-substituted 4-phenyl-1,2,3-triazoles here reported show π→π* absorption near 246 nm, in contrast to the 4-substituted 2-phenyl-1,2,3-triazoles (phenylosotriazoles), which absorb near 268 nm. The optical rotatory dispersion spectrum of 2 shows a negative Cotton effect and is closely similar to that of the 2-phenyl analog ( D- threo-pentulose phenylosotriazole).

Acetylenic sugar derivatives from glycals

D- lyxo-5-Hexyne-1,2,3,4-tetrol (II) was synthesized by reaction of 3,4,6-tri- O-acetyl-2-bromo- D-glucal (I) with butyllithium. Compound I was made from tri- O-acetyl- D-glucal via its dibromo adduct and treatment with triethylamine. The α- D- gluco form of the dibromo adduct is regarded as being the active participant in the dehydrobromination. D- threo-4-Pentyne-1,2,3-triol was similarly prepared from di- O-acetyl- D-xylal. II was acetylated to its tetraacetate (II-Ac), and hydrogenated to D- lyxo-1,2,3,4-hexanetetrol. II-Ac was hydrogenated to the hexanetetrol tetraacetate, which exhibited dimorphism. Ozonolysis gave tetra- O-acetyl- D-arabinonic acid and thus provides a new general method for preparing fully acetylated aldonic acids. The CCH part of II-Ac was readily hydrated to COCH 3, thus yielding an acyclic ketose derivative; but conditions were not found for effecting oxidative coupling of the copper(I) acetylide. Saponification of II-Ac (to II) was not accompanied by further cleavage of II into acetylene and D-erythrose. Lithium aluminum hydride converts 2,3-dibromotetrahydropyran into 3-bromotetrahydropyran, and changes the dichloride of tri- O-acetyl- D-glucal to 1,5-anhydro-2-chloro-2-deoxy- D-glucitol (and -mannitol). In the reduction of tetra- O-acetyl-α- D-glucopyranosyl bromide to tri- O-acetyl- D-glucal, some samples of zinc dust gave excellent yields, whereas other samples failed completely, even in the presence of some favored promoters.