Antonio Gómez-Sánchez

Protection of the amino group of amino sugars by the acylvinyl group: Part I, glycoside formation by the fischer reaction

Abstract 2-Deoxy-2-[(2,2-dimethoxycarbonylvinyl)amino]- ( 1 ) and 2-deoxy-2-[(2,2-diethoxycarbonylvinyl)amino]-α- d -glucopyranose ( 3 ), prepared in almost quantitative yields from the appropriate 3-alkoxy-2-alkoxycarbonylacrylic ester and 2-amino-2-deoxy- d -glucose hydrochloride, were used as N -protected derivatives in the preparation of glycosides by the Fischer procedure. Glycosidation of 1 with boiling methanolic hydrogen chloride afforded a mixture of methyl 2-deoxy-2-[(2,2-dimethoxycarbonylvinyl)amino]-α- ( 7α ) and -β- d -glucopyranoside ( 7β ), and minor amounts of methyl 2-deoxy-2-[(2,2-dimethoxycarbonylvinyl)amino]-α- d -glucofuranoside ( 18 ); 7α was easily isolated (55% yield). Using Amberlyst-15 (H + ) resin as catalyst, the proportion of the furanoside 18 was higher and 21% could be isolated. Reaction of 3 with hot ethanolic hydrogen chloride afforded a good yield of ethyl 2-deoxy-2-[(2,2-diethoxycarbonylvinyl)amino]-α- d -glucopyranoside. On the other hand, attempted glycosidations of 2-deoxy-2-[(2,2-diacetylvinyl)amino]-α- d -glucopyranose under similar conditions were unsuccessful. The 2,2-diacylvinyl group could be removed selectively under non-acidic conditions using chlorine, ammonia, or Amberlite IRA-400 (HO − ) resin.

Cleavage and oligomerization of malondialdehyde

Abstract Malondialdehyde (MDA) slowly self-condensates in aqueous solution at pH 4.5–6 and room temperature yielding (E)-(3′-oxo-1′-propenyl)malondialdehyde and 2,4-dihydroxymethylene-3-(2′-oxoethyl)glutaraldehyde. The latter compound exists in solution in equilibrium with 4-(1,3-dioxopropan-2-yl)-5-formyl-2-hydroxy-3,4-dihydro-2H-pyran, the trans-form of which can be readily isolated as a crystalline hemipotassium salt. Cleavage of MDA also occurs under these conditions leading to acetaldehyde, which further reacts with the excess of MDA to form 2,4-dihydroxymethylene-3-methylglutaraldehyde.

Highly efficient nitroaldol reaction promoted by trialkylsilyl chlorides

β-Nitroalcohols can be readily obtained in high yields by the one-pot reaction of aldehydes with nitrecompounds in the presence of Et3N, Bu4NF·3H2O and tBuMe2SiCl. Model experiments indicated that trialkylsilyl nitronic esters are not reaction intermediates.

Heterocycle formation from 1,3-dinitroalkanes. A novel pyrazole synthesis

Abstract 1,3-Dinitroalkanes, obtained in almost quantitative yields by Michael additions of nitroalkanes to nitro-olefins, react with hydrazines affording pyrazoles, in most cases in high yields.

Cleavage and oligomerization of malondialdehyde under physiological conditions

Abstract Malondialdehyde slowly oligomerizes in aqueous solution at pH 5-7 and room temperature. Cleavage of the dialdehyde also takes place under these conditions yielding ethanal, which further reacts with the excess of malondialdehyde to yield 2,4-dihydroxymethylene-3-methylglutaraldehyde.

Synthesis and glycosidation of 1-deoxy-1-[(2,2-diacylvinyl)amino]-d-fructoses☆☆☆

Abstract The reactions of 1-amino-1-deoxy- d -fructose acetate ( 1 ) with methyl 3-methoxy-2-methoxycarbonylacrylate and 5-methoxymethylene-2,2-dimethyl-1,3-dioxane-4,6-dione in the presence of a base afforded 1-deoxy-1-[(2,2-dimethoxycarbonylvinyl)amino]- ( 2 and 1-deoxy-1-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidenemethyl)amino]- d -fructose ( 3 ), respectively, in high yields. 1-Deoxy-1-[(4,4-dimethyl-2,6-dioxocyclohexylidenemethyl)amino]- d -fructose ( 4 ) was obtained (85%) by a transamination reaction between 1 and 5,5-dimethyl-2-phenylaminomethylene-1,3-cyclohexanedione in the presence of Et 3 N. The isomeric composition of equilibrium solutions of 1–4 was established by 13 C-n.m.r. spectroscopy. For all the compounds, the β-pyranose form was the main component in D 2 O; the α-furanose, the β-furanose, and, for 1 , the α-pyranose forms, were also present. The major constituents of 2 in (CD 3 ) 2 SO solution were the β- and the α-furanose forms. Acetylation of 2 afforded the tetra-acetates of the α- and β-furanose forms, the 3,4,6-triacetates of the α- and β-furanose forms, the 3,4,5-triacetate of the β-pyranose form, and 2,3,4,5,6-penta- O -acetyl-1-deoxy-1-[(2,2-dimethoxycarbonylvinyl)amino]- d - arabino -hex-1-enitol. Glycosidation of 2 with MeOHHCl afforded a mixture of methyl 1-deoxy-1-[(2,2-dimethoxycarbonylvinyl)amino]-α- ( 11α ) and -β- d -fructofuranoside ( 11β ), and methyl 1-deoxy-1-[(2,2-dimethoxycarbonylvinyl)-amino]-β- d -fructopyranoside ( 13 ). Compounds 11α and 13 were isolated as their tri-acetates ( 12 and 14 , respectively). Deacetylation and removal of the N -protecting group of 12 gave methyl 1-amino-1-deoxy-α- d -fructofuranoside (∼54% from 2 ).

Spectral properties and isomerism of nitroenamines. Part 4.1 (beta)-Amino-(alfa)-nitro-(alfa),(beta)-unsaturated ketones

A set of 4-alkyl(aryl)amino-3-nitrobut-3-en-2-ones (5), 4-ethylamino-3-nitropent-3-en-2-one (6), the related 3-alkyl(aryl)amino-2-nitro-2-cyclohexenones (7) with fixed geometry, and the N-deuteriated derivatives of some of them, were prepared and studied by vibrational (IR, Raman), NMR and, for some of the compounds, dynamic NMR spectroscopy. The spectra, considered together with the results of theoretical studies, provide a fairly accurate quantitative picture of the isomerism affecting 5 and 6. These compounds exist in solution as a mixture of the Z-isomer, having a strong hydrogen bond between the cis-related NO2 and the NH groups, in equilibrium with the E-isomer having a still stronger hydrogen-bond between the cis CO and NH groups. The proportions of the two isomers depend on concentration, solvent polarity, number of substituents around the CC bond and temperature, though the E-isomer is always the predominant one. The CH3CO group of the Z-isomers adopts, in the case of compounds 5, a planar s-cis conformation around the (C)C–C(O) single bond; in the case of the more sterically crowded compound 6, adopts a non-planar quasi-s-cis conformation. A low energy barrier between the configurational isomers was measured for compound 6 by dynamic 1H NMR spectroscopy. Vibrational couplings occur inside these strongly electron-delocalised systems, the extent of which depends on the molecular geometry, affecting mainly the ν(CC) and ν(C–N) modes, δ(N–H), and to a lesser extent ν(CO) and νa(NO2). The two isomeric forms can be readily distinguished and quantified by the spectra, and the energies of the intramolecular hydrogen bonds estimated by the large two-bond isotope effect, 2Δ13C(2/1H), observed on the C(1) chemical shifts on partially N-deuteriated samples. The spectral results for these compounds are discussed in comparison with those obtained for the simpler enaminones 1, nitroenamines 2, as well as for the related β-amino-α-nitro-α,β-unsaturated esters 4.

Vibrational spectroscopy and conformations of 2,2-diacylethenamines

The i.r., Raman, and 1H n.m.r. spectra of 2,2-diacetylethenamines (3) and 2-aminomethylene-5,5-dimethylcyclohexane-1,3-diones (4) show that these substances exist exclusively in the chelated enamino-diketone form, and that the conjugated system contained in them is essentially planar. The open-chain enamino-diketones (3) exist either in the solid state or in solution in the EZE-conformation (7). A similar conjugated core, having the fixed ZZE-conformation, contained in 5-aminomethylene-2,2-dimethyl-1,3-dioxane-4,6-diones (5) is most probably planar or nearly planar. The EZE- and ZZE- alignments of the enamino-diketones can be distinguished by their spectral properties, and particularly, by their vibrational spectra. Some features of the i.r. and Raman spectra indicate vibrational coupling between the two ν(CO) vibrations, the effect being more marked in the cyclic enamino-diketones (4) and -diesters (5) than in their open-chain analogues. On the other hand, the coupling of the ν(CO) with the ν(CC) and the δ(N–H) modes seems to be less efficient in these enaminodione systems than in the related simple enaninones. Further arguments are presented questioning the criteria established to ascertain the planarity of enamino-diones and of other enamines having two strong electron-acceptor groups at C-2.

Syntheses of (2-nitrovinyl)amino sugars and 2- and 3-(alditol-1-YL)-4-nitropyrroles

Abstract Reactions of 2-amino-2-deoxy- d -glucose and its N -butyl derivative with 1-ethoxy-2-nitroethene produced 2-deoxy-2-[(2-nitrovinyl)amino]- d -glucose ( 6 ) and its N -butyl derivative ( 8 ), respectively, in high yields. The spectra of these compounds indicated that they were α,β-anomeric mixtures, and also that 6 existed as equilibrium mixtures of the Z - and E -geometrical isomers, the proportions of which depended on the polarity of the medium. Acetylation of 6 and 8 afforded the corresponding tetra-acetates 7 and 9 . The reaction of β- d -glucopyranosylamine with 1-ethoxy-2-nitroethene yielded syrupy 1-(β- d -glucopyranosylamino)-2-nitroethene, which was characterised as the crystalline tetra- O -acetyl derivative. Compounds 6 and 8 cyclised readily to give the 4-nitro-2-( d - arabino -tetritol-1-yl)pyrroles 12 and 14 , which could also be obtained by treatment of 2-amino-2-deoxy- d -glucose and its N -butyl derivative with 1-ethoxy-2-nitroethene in boiling methanol. Similar reactions with 1-amino-1-deoxy- d -fructose and its N -methyl, N -butyl, and N - p -tolyl derivatives afforded the respective 4-nitro-3-( d - arabino -tetritol-1-yl)pyrroles. A series of 4-nitro-3- and -2-pyrrolecarbaldehydes was obtained by periodate oxidation of the 2- and 3-(alditol-1-yl)-4-nitropyrroles.

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.