Amparo López-Castro

Reaction of 2-amino-2-deoxy-d-glucose with aryl and acyl isothiocyanates, and aryl isocyanates: structure of the intermediate products

Abstract The structure of (4 R )-1-aryl-5-hydroxy-4-( d - arabino -tetritol-1-yl)imidazolidine-2-thiones ( 1–3 ), obtained by reaction of 2-amino-2-deoxy- d -glucose with aryl isothiocyanates, has been confirmed by 1 H- and 13 C-n.m.r. spectroscopy. Likewise, the structures of 2-(3-benzoylthioureido)-2-deoxy- d -glucopyranose and 2-deoxy-2-(3-phenylureido)- d -glucopyranose, prepared by reaction of 2-amino-2-deoxy- d -glucose with benzoyl isothiocyanate and phenyl isocyanate, respectively, were also established. An X-ray analysis of 1 –5 R (aryl = phenyl) has been carried out and its conformation in the solid state is one of the preponderant conformations in solution.

Synthesis and crystal structure of methyl 2-amino-2,6-dideoxy-α-d-glucopyranoside-6-sulfonic acid

Abstract Methyl 2-amino-2-6-dideoxy-α- d -glucopyranoside-sulfonic acid (8) was prepared by oxidation of methyl 3,4-di-O-acetyl-6-S-acetyl-2-benzamido-2-deoxy-6-thio-α- d -glucopyranoside with hydrogen peroxide in acetic acid followed by N- and O-deacylation with aqueous sodium hydroxide. Compound 8 was also obtained by oxudation of methyl 3,4-di-O-acetyl-6-S-acetyl-2-deoxy-2[(2,2-dimethoxycarbonyl-vinyl) amino]-6-thio-α- d -glucopyranoside followed by deacetylation with Amberlite IR-120 (H+) resin. An X-ray analysis of 8, crystallised as a dihydrate, was carried out.

Regio- and stereoselective synthesis of 3- and 5-(C-glycosyl)-4-nitroisoxazolidines by nitrone–nitroalkene [3+2] cycloaddition reactions

Abstract Cycloaddition reactions of nitrones, including sugar nitrones, with nitroalkenes, including sugar nitroolefins, led with complete regioselectivity and stereospecificity to 4,5- trans -4-nitroisoxazolidines in 51–78% global yields. The endo/exo stereoselectivity depends on the type of sugar derivative used. As expected, the best π-diastereofacial selectivity was observed when both partners were sugar derivatives. Isomerisation of the first formed diastereomers by the action of silica gel was observed in some cases. Absolute configurations for two crystalline products were assigned by X-ray diffraction methods.

Branched-chain fluoro nitro d- and l-sugars from glucose

Abstract Mixed crystals of methyl 3-deoxy-3- C -methyl-3-nitro-α- d - and β- l -glucopyranosides (1:1), easily available from d -glucose by means of the Baer reaction, were completely characterised by X-ray diffraction analysis. These diastereomeric components, separation of which could be achieved through their 4,6- O -benzylidene derivatives, were selectively fluorinated at position 6 by treatment with DAST and stereoselectively transformed into phenyl 3-deoxy-3- C -methyl-3-nitro-1-thio-β- d -glucopyranoside and phenyl 3-deoxy-3- C -methyl-3-nitro-1-thio-β- l -glucopyranoside, respectively. Fluorination with DAST of each pure enantiomer afforded, depending on the conditions, the corresponding enantiomeric phenyl 3,6-dideoxy-6-fluoro-3- C -methyl-3-nitro-1-thio-β- d - and β- l -glucopyranosides or the respective rearranged 2,3,6-trideoxy-6-fluoro-3- C -methyl-3-nitro-2-phenylthio-α- d - and α- l -mannopyranosyl fluorides. This route constitutes a simple method for obtaining fair-to-good yields of 6-fluorinated branched-chain d - and l -sugar derivatives, potentially useful as glycosyl donors, starting from d -glucose.

A novel highly diastereoselective synthesis of chiral dihydrothiophenes from mesoionic compounds

Thioisomunchnones undergo 1,3-dipolar cycloaddition with chiral nitroalkenes to afford stereoselectively 4,5-dihydrothiophenes by means of an unprecedented fragmentation of cycloadducts; the structures of these products have been established by single crystal X-ray structure analyses.

A new synthesis of 6-oxopyrimidinium-4-olates. Theoretical study of the regioselective cycloaddition of arylisocyanates with a 1,3-thiazolium-4-olate system

Abstract A new and regioselective synthesis of 6-oxopyrimidinium-4-olate systems ( 13–21 ) is described, involving the 1,3-dipolar cycloaddition of the 1,3-thiazolium-4-olate 12 with arylisocyanates. MNDO and AM1 calculations rationalise the reactivity and regioselectivity experimentally observed.

Studies on sugar nitro-olefins. Part 7. Synthesis of 3-(alditol-1-yl)-1,2,3,5,6,7-hexahydro- and -1,5,6,7-tetrahydro-indol-4-ones. X-Ray molecular structure of (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-one

Raney nickel reduction of (3R)-2-hydroxyimino-3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-gluco-pentitol-1-yl)-3,5,6,7-tetrahydrobenzofuran-4(2H)-ones (5) gives (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-galaco-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-ones (6) in high yields. Deacetylation of compounds (6) with catalytic sodium methoxide in methanol affords the corresponding (pentitol-1-yl)indolones (7). Compounds (6) can be transformed into the 3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-gluco-pentitol-1-yl)-1,5,6,7-tetrahydroindol-4-ones (8) by treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The structure of (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-one (6a) was confirmed by an X-ray structure determination.

Synthesis of new C-sulfosugars and C-sulfoalditols: Amadori rearrangement of 6-C-sulfo-d-fucose

Abstract The novel 6-deoxy-6-C-sulfo- d -galactose (6-sulfofucose) potassium salt was prepared by oxidation of 1,2,3-tri-O-acetyl-6-S-acetyl-4-O-benzoyl-6-deoxy-α- d -galactopyranose with hydrogen peroxide and potassium acetate in acetic acid. Its cyclohexylammonium salt underwent a spontaneous conversion into 1-cyclohexylamino-1,6-dideoxy- d -tagatofuranose-6-C-sulfonic acid 4 through an Amadori rearrangement. 6-Deoxy-6-C-sulfo- d -glucose (sulfoquinovose) and 6-deoxy-6-C-sulfo- d -galactose were transformed into the corresponding 6-deoxy-6-C-sulfoalditols and 1-amino-1,6-dideoxy-6-C-sulfoalditols by reduction and reductive amination, respectively. The α anomeric configuration of 4, crystallised as the monohydrate, was assigned by X-ray crystallographic analysis. A conformation between E5 and 4T5 for the sugar ring, stabilised by a strong intramolecular hydrogen bond between NH and O-4, was observed.

Silica gel-catalysed addition of methyl nitroacetate to 1,2: 3,4-di-O-isopropylidene-α-d-galacto-hexodialdo-1,5-pyranose and 2,3-O-isopropylidene-d-glyceraldehyde. Crystal structure of methyl 7-acetamido-7-deoxy-1,2 : 3,4-di-O-isopropylidene-l-threo-α-d-galacto-octopyranuronate

Abstract The addition of methyl nitroacetate to 1,2:3,4- di -O- isopropylidene-α- d -galacto- hexodialdo-1,5-pyranose (5) and to 2,3-O- isopropylidene- d -glyceraldehyde (6) in the presence of silica gel led stereoselectively to the formation of only (from 5) or mainly (from 6) two of the four possible nitroaldols in high yield. The catalytic action of silica gel was required in the reaction of 6, but not in that of 5. Isolation of a crystalline, reduced and N -acetylated derivative from the mixture of nitroaldols (7 + 8) obtained from 5 allowed for the determination of its crystal structure, showing that it has the 6 R , 7 R absolute configuration (one of the two possible 6,7- threo configurations) by X-ray diffraction methods. Therefore, the same 6 R configuration was also assigned to the nitroaldols 7 and 8, which on the basis of the easy α-epimerisation of the α-nitro esters should differ only in the configuration at C-7. A pair of amino alcohols obtained from the same mixture of nitroaldols were separately transformed into a 4,5- cis - and a 4,5- trans -oxazoline, the configurations of which were correlated with the C-6,7 relative configuration of the respective amino alcohols and also the respective nitroaldol. The Felkin model explained the high stereoselectivity observed. The configurations of the two predominant nitroaldols obtained from 6 were tentatively assigned by applying the Felkin model.

Towards cyclic, conformationally constrained, fluorine-containing β-amino acid derivatives from d-glucose

Abstract Novel, potentially bioactive, fluorinated branched-chain monosaccharides were obtained by reaction of diethylaminosulphur trifluoride (DAST) with a series of methyl 3- C -cyano-3-ethoxycarbonyl-β- d -glucopyranoside derivatives, including the 4,6- O -benzylidene derivative and their 3- C -( N -protected aminomethyl) reduction products, as well as the phenyl 3- C -cyano-3-ethoxycarbonyl-1-thio-α- d -(and β- d -)glucopyranosides. The absolute configuration at C(3) was unambiguously assigned for all compounds on the basis of X-ray crystallographic analysis of methyl 4,6- O -benzylidene-3- C -cyano-3-deoxy-3-ethoxycarbonyl-β- d -glucopyranoside, corroborating the previous tentative assignment by other authors for the 4,6-unprotected compound. The course of the fluorination depended on the reaction temperature and the substitution pattern of the substrate. Thus, for methyl 3- C -cyano-3-ethoxycarbonyl-β- d -glucopyranoside, fluorination occurred exclusively at C(6), but for the phenylthio analogue, a 2-deoxy-2-phenylthio-α- d - manno -configured glycosyl fluoride and its 6-fluoro derivative were obtained, resulting from the expected rearrangement reaction, whilst starting from the phenylthio α anomer, only the unrearranged 6-fluoro compound was formed. Rearrangement was also observed in the fluorination of methyl 4,6- O -benzylidene-3- C -( N -protected aminomethyl)-β- d -glucopyranoside, which led to the 2- O -methyl-α- d -mannopyranosyl fluoride derivative as the sole product. This methodology may constitute a simple route to enantiopure conformationally constrained cyclic fluorinated β-amino acids having the α carbon atom shared with a pyranose ring, although only moderate yields were achieved, particularly in the fluorination step.