SYNTHESIS OF NEW OXAMIDE DERIVATIVES OF D-GLUCOSAMINE AND ALIPHATIC OR AROMATIC AMINES

New oxamides, derivatives of D-glucosamine and aliphatic or aromatic amines were prepared by acylation of methyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α- or -β-D-glucopyranoside (1c or 1d) with oxalyl chloride, followed by reaction with amine. The reaction was assumed to proceed by the intermediate of N-carbomethoxy N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α or β-D-glucopyranosid-2-yl) oxamic acid chloride which reacted with amines, and afforded N-acetyl, N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (5–7), and N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (8–13).     

Approaches to intramolecular sialylation. 2. Synthesis of per-O-acetylated thioglycosides of N-acetylneuraminic acid containing an unprotected carboxy group

Various approaches to the synthesis of per-O-acetylated thioglycosides of N-acetylneuraminic acid (Neu5Ac) containing an unprotected carboxy group starting from the corresponding methyl esters were comparatively studied. One-step demethylation of methyl thioglycoside (LiI, Py, reflux) proceeded inefficiently in contrast to the analogous smooth reaction of phenyl thioglycoside. An indirect route to derivatives with a free carboxy group involving saponification followed by acetylation of hydroxy groups proved to be more efficient for methyl -thioglycoside of Neu5Ac.     

N,N′-Diacylated imidazolidines and hexahydropyrimidines

A method for the preparation ofN-monoacyl imidazolidines and hexahydropyrimidines (as hydrochlorides) by interaction of monoacylated derivatives of ethylenediamine and trimethylenediamine with chloromethyl methyl ether was developed. Also a method for the preparation ofN,N-diacylimidazolidines and hexahydropyrimidines either by acylation of their monoacyl derivatives or by reaction of the correspondingN,N-diacyl alkylenediamine derivatives with dimethoxymethane, diacetoxymethane, 1,3,5-trioxane or chloromethyl methyl ether was designed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1452–1456, August, 1994.     

SYNTHESIS OF ALKYL N-CYANO-N-SUBSTITUTED CARBAMATES AND N,N-DISUBSTITUTED CYANAMIDES1

Abstract

The reactions of S,S' methyl cyanodithioimidocarbonate with potassium hydroxide in alkyl or benzyl alcohol furnished the O-alkyl and benzyl O-potassium cyanoimidocarbonates (1–5). The reaction of the potassium salts (1,3, or 4) with a 10% excess of alkyl, allyl or benzyl halides afforded the unknown titled carbamates (6–17). The reaction of 2 with 10% excess benzyl bromide or 5 with 10% excess methyl iodide gave the same product, N-benzyl-N-methyl cyanamide (18). The reactions of 2 with 10% and 55% excess allyl bromide afforded N-allyl-N-methyl cyanamide (19) and N,N-diallyl cyanamide (20), respectively. The reaction of 3 with 28% excess of allyl iodide furnished N-allyl-N-propyl cyanamide (21).

Possible mechanisms and supporting NMR, IR and mass spectra data are discussed.     

Concurrent synthesis of vanillin and isovanillin

A method for concurrent synthesis of vanillin and isovanillin has been developed by a nonregioselective Vilsmeier–Haack reaction of O-alkyl guaiacols. O-Alkylation of guaiacol provided the corresponding O-alkyl guaiacol (1), which was then formylated with N-methylformanilide/phosphorus oxychloride to give a mixture of 4-alkoxy-3-methoxy-benzaldehyde (2) and 3-alkoxy-4-methoxybenzaldehyde (3). Finally, the obtained mixture underwent a selective dealkylation by anhydrous aluminium trichloride, while leaving methyl groups intact to simultaneously achieve the significant fine chemicals vanillin and isovanillin.     

Synthesis of 1,3,4-thiaza- and 1,3,4-oxazaphosphol-2-lines based onN-phosphorylated (thio)ureas

The reactions ofO-phenyl chloromethylisothiocyanatothioxophosphonate andO-phenyl chloromethylisocyanatophosphonate with trimethylsilyldiethylamine lead to the formation of 1,3,4-thiazaphosphol-2-ine and 1,3,4-oxazaphosphol-2-ine, respectively. Phosphorylation ofN-methyl-N-phenyl-N,N-bis(trimethylsilyl)urea withO-phenyl chloromethylchlorophos phonate gives 1,3,4-diazaphospholidin-2-one.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1857–1859, July, 1996.     

Reaction of 2,3-O-Isopropylidene-D-Glyceraldehyde and Some Dialkyl and Diarylthiomethyl Sulfoxides: Stereochemical Aspects

Abstract

The reaction of 2,3-O-isopropylidene-D-glyceraldehyde with different dialkyl and diarylthiomethyl sulfoxides occurs with a high selectivity and produces the corresponding 1-alkyl(or l-aryl)-sulfynil-l-alkyl(or 1-aryl) thio-3,4-O-isopropylidene-D-tetroses as pure diastereoisomers. We have determined the absolute configuration of the three chiral centers formed in these reactions.     

Fungizide Pyridinderivate, 2. Mitt.: Derivatisierung von α-Trichlormethyl-3-pyridinmethanol

Summary The antifungal lead structure -trichloromethyl-3-pyridinemethanol (1 a) was modified and esters, (thio-)carbamates, and sulfonates as well as other derivatives incorporating the pyridylcarbinol structure were prepared. The optical resolution as well as the N-oxidation of1 a are described.

     

Synthesis and physiological activity of trialkyl phosphorothioates and trialkyl phosphorodithioates containing fragments of N-acylated amino acids

A series of S-[N-acyl-N-(alkoxycarbonylalkyl)aminomethyl] O,O-dialkyl phosphorothioates and -dithioates were prepared by the reactions of the corresponding alkali salts of dialkyl phosphorothioates or dialkyl phosphorodithioates with esters of N-acyl-N-(chloromethyl)glycine or N-acyl-N-(chloromethyl)--alanine and by the reactions of dialkylphosphorothioic or dialkylphosphorodithioic acids with N-acylated amino acids or their esters and paraformaldehyde in the presence of gaseous HCl. Some of the resulting compounds proved to be active permethrine synergists.     

Determination of thermodynamic functions of sorption for cyclohexyl-, piperidyl-, morpholyl-, and thiomorpholyl-n-alkanes by capillary gas-liquid chromatography

The values of partial molar free energy (G), enthalpy (H), and entropy (S) of sorption in the homologous series ofN-alkylpiperidines,N-alkylmorpholines,N-alkyl thiomorpholines, and alkylcyclohexanes were determined. It was found that the free energy of sorption is determined to a greater extent by the enthalpy term than by the entropy one. The free energy of sorption of the first homolog decreases when then-alkyl chain is attached directly to the carbon atom of the cycle and increases in the case ofN-alkylsubstituted heterocycles. The influence of the heteroatom nature on intermolecular interactions of homologs with the nonpolar stationary phase was quantitatively estimated on the basis of thermodynamic data.Dead time necessary for calculation of the retention factor was determined by the retention of methane injected into the column simultaneously with the sample.Translated from Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 2030–2032, August, 1996.     

Separation of Enantiomers of N-Protected Non-Protein Amino Acid Esters by Chiral High-Performance Liquid Chromatography

The high-performance liquid chromatographic separation of enantiomers of N-protected non-protein amino acid esters was investigated by using a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase column (Daicel Chiracel OD). The effect of the N-protecting groups and the ester groups on chiral discrimination was examined. The benzyloxycarbonyl (Z), 4-methoxybenzyloxycarbonyl, and 9-fluorenylmethoxycarbonyl derivatives gave good enantiomeric separations, while the formyl and t-butoxycarbonyl groups marred them. Almost all the alkyl esters examined and the benzyl ester gave enantiomeric separations better than or of the same order as the methyl ester. The N-Z-protected methyl esters of a number of non-protein -amino acids were well resolved using hexane–2-propanol as a mobile phase. The resolution of -amino acid derivatives was inferior to that of the isomeric -amino acid derivatives.     

Chemistry of N,N-bis(silyloxy)enamines. 4. Study of the reactions of N,N-bis(silyloxy)enamines with 1,3-diones

Smooth C,C-cross-coupling of N,N-bis(silyloxy)enamines with methyl malonates gives the corresponding methyl -hydroxyiminoalkylmalonates.     

Regioselectivity of Alkylation of 3-Substituted 5-Amino-1,2,4-thiadiazoles

We have synthesized 3-substituted 4-alkyl-5-imino-4,5-dihydro-1,2,4-thiadiazoles by reaction of 3-alkyl(benzyl)thio-5-amino-1,2,4-thiadiazoles with methyl iodide or ethylene chlorohydrin. In the reaction with epichlorohydrin, addition of an oxirane molecule occurs with formation of tetrahydropyrimido[2,1-b]-1,2,4-thiadiazoles.     

First synthesis of 2-[alkylamino(diethoxyphosphoryl)methyl]acrylic ethyl esters

The ethyl α-bromomethyl-β-(diethoxyphosphoryl)acrylic acid ester 9 has been prepared by addition of bromine to allylphosphonate 7 then dehydrobromination with DBU in acetonitrile. Reaction of allylic bromide 9 with primary amines in a bimolecular S_N2′-type mecanism in methanol at low temperature, gives rise to the 2-[alkylamino(diethoxyphosphoryl)methyl]acrylic acid ethyl esters 6.     

Strukturelle Abwandlungen anN-Acetylneuraminsäure, 4. Mitt. Transformationen am Diethyl-dithioketal desN-Acetylneuraminsäure-γ-lactons

Partial protection of diethyldithioketal ofN-acetylneuraminic acid--lactone using one or two equivalents oft-butyldimethylchlorosilane leads to the 9-O-silyletherderivative7 and the 8,9-bis-O-silylderivative5, resp. The reaction of1 as well as7 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (TIPSiCl₂) yields selectively the protected products4 and9. The 9,8,7,6-tetra-O-acetyl-N-acetylneuraminic acid--lactone derivative3 is formed by the oxidative desulfurazation of the peracteylated form of1 (i. e.2) by means ofNBS. By reaction of5 withTPPDEAD the 6,7-carbonato compound6 arises instead of the expected 6,7-epoxyderivative. The analogous carbonate8 is formed by treating7 with bisimidazolylcarbonate.

     

One-pot facile conversion of Baylis-Hillman adduct into N-alkyl 3-(E)-alkylidene-5-substituted sulfonylpiperidine-2,6-dione. Formal synthesis of tacamonine

A stepwise [3+3] strategy to N-alkyl 3-(E)-alkylidene-5-substituted sulfonylpiperidine-2,6-dione 1 used various N-alkyl α-substituted sulfonylacetamides 2 and α,β-unsaturated esters 3 as starting materials. α,β-Unsaturated esters 3 were generated by Baylis-Hillman reaction. A ring closure mechanism was proposed for the reactions. This method provides a convenient formal synthesis of tacamonine.     

Synthesis and Biological Activities ofN-Acetyl-6-O-acyl-1-thiomuramoyl-l-alanyl-d-isoglutamine Derivatives

A variety of N-[2-O-(2-acetamido-6-O-acyl-1-S-acyl-2, 3-dideoxy-1-thio-β3-D-glucocyranose-3-yl)-D-lactoyl]-L-alanyl-D-isoglutamine methyl esters were synthesized. Their immunoadjuvant activities were examined in guinea-pigs.     

Tetrachlorosilane-Sodium Azide System in the Synthesis of Tetrazole-Containing Amino Acid Derivatives

Treatment of N-acetyl-(RS)-phenylalanine and N-acetyl-(RS)-leucine methyl esters with the system tetrachlorosilane-sodium azide leads to formation of tetrazole-containing amino acid derivatives. The latter can be converted into -substituted 5-methyl-1-tetrazolylacetic acids and the corresponding bis-tetrazoles.     

Monofluoration stereoselective par le phenyltetrafluorophosphorane (PhPF4) Part. II. Application a la synthese des isomeres thréo et érythro des alkyl-2 fluoro-3 phenylpropanoates de methyle. Analyse conformationnelle par R.M.N. de 19F et 1H.

The stereoselective fluorination of four couples of diastereoisomeric 2-alkyl 3-hydroxy 3-phenylpropanoic methyl esters

by the reaction of the phenyltetrafluorophosphorane with the corresponding trimethylsilylethers derivatives

is described. The structure of the 2-alkyl 3-fluoro 3-phenyl propanoic methyl esters

obtained quantitativly has been determined unambiguously by NMR analysis. ¹⁹F NMR results permit us to determine the relative populations of the rotamers for each of the isomers threo and erythro.     

[4+2] Cycloaddition reactions of 4-sulfur-substituted 2-pyridones with electron-deficient dienophiles

[4+2] Cycloaddition reactions of 4-(phenylthio)-1-tosyl-2-pyridone (6a) and 4-(phenylsulfonyl)-1-tosyl-2-pyridone (6b) with electron-deficient dienophiles 7 (N-methylmaleimide, N-phenylmaleimide, and methyl acrylate) gave new isoquinuclidine products 8-10. The N-tosyl group of 6a and 6b was also efficiently converted to N-alkyl derivatives 6c-f, which showed different stereoselectivity toward reactions with dienophiles 7. Several other dienophiles 15 (dimethyl acetylenedicarboxylate, methyl vinyl ketone, ethyl vinyl ether, and methyl methacrylate) were found not to react with 6a or 6b, but led to the formation of tosyl migration products 4-(phenylthio)-O-tosyl-pyridinol (16a) and 4-(phenylsulfonyl)-O-tosyl-2-pyridinol (16b), respectively. The reactivity, regioselectivity, and stereoselectivity of the cycloaddition reactions were also compared with semi-empirical calculations.