Simeón Pérez-Garrido

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.

Lengthening of the carbon chain of sugars by the Ch(NO2·CH(OEt)2 fragment a route to higher 2-amino-2-deoxyaldoses☆

Abstract Nitroaldol (Henry) reactions promoted by trialkylsilyl chlorides have been applied to the preparation of chain-extended nitro and amino sugars. The one-pot reaction of 1,2:3,4-di O -isopropylidine-α- d - galacto -hexodialdo-1, 5-pyranose ( 1 ) with 1,1-diethoxy-2-nitroethane in the presence of Et 3 N, Bu 4 NF ·3H 2 O, and t BuMe 2 SiCl yielded 7-deoxy-1,2:3,4-di- O -isopropylidene-7-nitro- l - threo-α- d -galacto -octodialdo-1, 5-pyranose diethyl acetal ( 3a ) and a diastereoisomer in the ratio 4:1. The structure of 3a was established by a single crystal X-ray diffraction study. Hydrogenation of 3a (Ni, H 2 ) afforded the corresponding 7-amino-7deoxyl-1,2:3,4-di- O -isoprpylidene- l - threo-α- d -galacto -octodialdo-1,5-pyranose diethyl acetal 4a ). Conversion of the latter compound into a trans -oxazoline derivative demonstrated that the l - threo configuration had been retained. Likewise, reaction of the aldehydo sugar 1 with 1-nitropropane was carried out in order to compare the efficiency of the new nitroaldol procedure here applied with that reported using trialkylsilyl nitronic esters as intermediates.

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.

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.

Higher glycosamino acid precursors: C7 and C8 aminodialdoses via regio- and stereoselective [3+2] cycloaddition of vinyl trimethylsilane to C-glycosyl nitrones

Abstract Protected C 7 and C 8 aminodialdoses were prepared stereoselectively from readily available C 5 and C 6 monosaccharide N -benzyl nitrones, by regio- and diastereoselective 1,3-dipolar cycloaddition reactions with vinyl trimethylsilane, followed by acetyl chloride-mediated cleavage of the 5-(trimethylsilyl)isoxazolidine formed. The cycloaddition reaction took place in moderate to good global yields (67–74%); estimation of diastereoselectivities from isolated yields showed total endo preference for the reaction of the d - galacto configured nitrone and high endo preference for the d - ribo analogue, but exo preference for the d - xylo configured substrate. Attack on the re face of the nitrone was predominant in all cases. The absolute configuration of one of the protected 3-(α- d - galacto -pentopyranos-5-yl)isoxazolidine products was assigned by X-ray crystallographic analysis, allowing correlation of the configuration at the new stereogenic centre in the corresponding aminodialdose. For non-crystalline isoxazolidines, configurations were assigned on the basis of NOESY experiments and/or chemical correlation. Combined yields of aminodialdoses coming from isoxazolidines having identical configuration at C(3) sometimes reached high values (up to 90%). These compounds are precursors of higher-chain glycosamino acids.

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.

Synthesis and characterization of a salt of sodium with L-malic acid: A new ferroelectric?

A new inorganic malate salt NaL-Malic acid has been synthesized. Elemental analysis suggests that the compound has the empirical formula NaC4H5O5. This compound is presumed to be analogous to tartrate salts, which have interesting nonlinear optical and ferroelectric properties. The extensively investigated Rochelle salt is a salt of sodium and potassium with tartaric acid and has interesting ferroelectric properties. Preliminary thermal and dielectric measurements of the NaL-Malic acid salt show the existence of three reversible phase transitions located approximately at the following temperatures 310 K, 325 K and 360 K. The lattice parameters for the crystal structure at room temperature, obtained from X-ray powder diffraction, are also reported.

Spectroscopic and X-ray crystallographic studies of the potassium salt of hexameric malondialdehyde

Abstract The crystalline potassium salt of a hexameric form of malondialdehyde has been obtained and shown to be racemic potassium hydrogen bis [trans-4-(1,3-dioxopropan-2-yl)-5-formyl-2-hydroxy-3,4-dihydro-2H-pyran].

Diethyl 6(R)-3-(4-chlorophenyl-6-(tetra-O-acetyl-D-arabino-threitol-1-yl)-1,2,3,6-tetrahydro-1,2,3,4-tetrazine-1,2-dicarboxylate, C26H33ClN4O12

The configurations around the chiral centres C53, C52, C51 and C5 are R, S, R and R, respectively, corresponding to a D-arabino conformation. The tetrahydrotetrazine ring has a conformation close to that of a half-boat. Packing of the molecules is governed by normal van der Waals contacts