Approaches to intramolecular sialylation. 3. Synthesis of 2,4-dimethoxybenzyl ester of per-O-acetylated N-acetylneuraminic acid thioglycoside and its attempted oxidation with DDQ in the presence of nucleophiles

2,4-Dimethoxybenzyl ester of per-O-acetylated N-acetylneuraminic acid thioglycoside was synthesized and attempts at the oxidative (DDQ-induced) addition of O-nucleophiles (water and galactose derivatives with unprotected hydroxy group at C(6)) to the benzylic carbon atom of this ester were made.     

Approaches to intramolecular sialylation. 1. Synthesis of pseudodisaccharide Neu5Ac-(1-2)-Gal with ester-linked monosaccharide residues

An efficient approach was developed for ester-linking the sterically hindered carboxy group of N-acetylneuraminic acid with the secondary hydroxy group at C(2) of galactose. Putative precursors of the glycosidically linked disaccharide Neu5Ac-(2-3)-Gal were prepared.     

Conversion of N-acetylneuraminic acid glycosyl chloride into dibenzyl glycosyl phosphate: O-glycosylation in the absence of a promoter

Readily accessible N-acetylneuraminic acid (Neu5Ac) glycosyl chloride, which was regarded to be a poor glycosyl donor, was shown to react with dibenzyl phosphoric acid salts in the absence of glycosylation promoters to give the corresponding -Neu5Ac dibenzyl glycosyl phosphate in high yield.     

Selective preparation of glycosyl sulfone or glycal by treatment of phenyl thioglycoside of N-acetylneuraminic acid with m-chloroperbenzoic acid

Treatment of acetylated phenyl thioglycoside of N-acetylneuraminic acid with m-chloroperbenzoic acid (MCPBA) in CH₂Cl₂ affords quantitatively mixtures of the respective sulfone and glycal free from the sulfoxide. The outcome of the reaction does not depend on the anomeric configuration of the starting thioglycoside. The sulfone can be selectively prepared (yield 100%) by oxidation with an excess of MCPBA and NaHCO₃. In the presence of pyridine (2 equiv.) and MCPBA (2 equiv.), the major product is glycal (yields 81—88%). This version of the reaction can be regarded as a new method for the preparation of sialic acid glycals.     

Gangliosides from the starfishEvasterias echinosoma: identification of a disialoganglioside containing 8-O-methyl-N-acetylneuraminic acid andN-formylgalactosamine

Gangliosides were isolated from the starfishEvasterias echinosoma and their structures were elucidated by chemical and physicochemical methods. Two major gangliosides were found to be disialogangliosides, whose carbohydrate chain is based on the trisaccharide β-N-acylgalactosaminyl-(l→3)-β-galactosyl-(l→4)-β-glucose (acyl is formyl or acetyl), both residue at of 8-O-methyl-N-acetylneuraminic acid being attached to theN-acylgalactosamine residue at positions 3 and 6. The minor components are disialogangliosides with linear carbohydrate chains in which the terminal sialic acid residue is attached to the penultimateN-acetylneuraminic acid residue at positions 4, 8, or 9. The lipid part of the gangliosides consists of sphingenine and unsubstituted fatty acids (mainly, palmitic and stearic acids). Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 156–161, January, 2000.     

Gangliosides from the starfishEvasterias echinosoma: identification of a disialoganglioside containing 8-O-methyl-N-acetylneuraminic acid andN-formylgalactosamine

Gangliosides were isolated from the starfishEvasterias echinosoma and their structures were elucidated by chemical and physicochemical methods. Two major gangliosides were found to be disialogangliosides, whose carbohydrate chain is based on the trisaccharide β-N-acylgalactosaminyl-(l→3)-β-galactosyl-(l→4)-β-glucose (acyl is formyl or acetyl), both residue at of 8-O-methyl-N-acetylneuraminic acid being attached to theN-acylgalactosamine residue at positions 3 and 6. The minor components are disialogangliosides with linear carbohydrate chains in which the terminal sialic acid residue is attached to the penultimateN-acetylneuraminic acid residue at positions 4, 8, or 9. The lipid part of the gangliosides consists of sphingenine and unsubstituted fatty acids (mainly, palmitic and stearic acids). Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 156–161, January, 2000.     

Synthesis of N-glycoconjugates of glycyrrhetic acid

New N-glycoconjugates that are analogs of glycyrrhizic acid were synthesized by condensation of α-L-rhamnopyranosylamine and β-D-lactosylamine with acid succinate and phthalate of glycyrrhetic acid methyl ester using N,N′-dicyclohexylcarbodiimide (DCC) or DCC-N-hydroxybenzotriazole. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 54–56, January–February, 2006.     

Sulfur ylides 13. Synthesis and intramolecular cyclization of keto-stabilized sulfur ylides

Keto-stabilized sulfur mono-and bisylides were obtained from N-phthalylglutamic acid and their intramolecular cyclization was studied. The intramolecular cyclization of the ylide obtained at the α-carboxy group gave a product of the pyrrolizidinedione structure; bisylide yielded a cycloheptene derivative as the result of intramolecular recombination of intermediate dicarbene. The ylide obtained at the γ-carboxy group underwent no cyclization, giving methylthio ketone and oxo benzoate. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2771–2776, December, 2005.     

Extending the possibility of an N-Troc-protected sialic acid donor toward variant sialo-glycoside synthesis

The potential of an N-Troc-protected sialic acid donor, equipped with phenylsulfenyl functionality as a leaving group, has been explored. As a result, the entitled donor was proven to be highly reactive and to have broad applicability toward the synthesis of variant sialo-glycans, which have N-glycolyl, de-N-acetyl, 1,5-lactam and 8-O-sulfo sialic acid analogs.     

Synthesis of N-nitrooxazolidines and N-nitrotetrahydro-1,3-oxazines from N-(2-hydroxyalkyl)- and N-(3-hydroxyalkyl)sulfamates

A method was developed for the preparation of functionally substituted N-nitrooxazolidines and N-nitrotetrahydro-1,3-oxazines by nitration of the products obtained in the reactions of N-(2-hydroxyalkyl)- and N-(3-hydroxyalkyl)sulfamates with formaldehyde.     

Direct synthesis of hetero-biaryl compounds containing an unprotected NH2 group via Suzuki-Miyaura reaction

Hetero-biaryl compounds were prepared via the Suzuki-Miyaura coupling reaction of hetero-aryl moieties containing an unprotected NH₂ group and arylboronic acids. D-t-BPF was found to be an efficient ligand for the cross-coupling of NH₂-unprotected hetero-aryl chlorides with phenylboronic acid.     

Synthesis of 1,2-azaphospholanes containing an amino acid fragment

2-Oxo-1,2-azaphospholanes and 1,2-azaphospholanium salts containing an amino acid fragment were synthesized by intramolecular P-alkylation of N-3-chloropropyl-substituted tricoordinate phosphorus amides. Hydrolysis of 2-oxo-1,2-azaphospholanes at the P-N bond gives rise to γ-aminopropylphosphonic acid derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2557–2562, November, 2005.     

Synthesis of 1,2,3,4-tetrazino[5,6-g]benzo-1,2,3,4-tetrazine 1,3,7,9-tetraoxides

1,2,3,4-Tetrazino[5,6-g]benzo-1,2,3,4-tetrazine 1,3,7,9-tetraoxides, which possess an-thracene-type annulation of the benzene ring with two 1,2,3,4-tetrazine 1,3-dioxide fragments, were obtained for the first time from aminobenzenes containing tert-butyl-NNO-azoxy groups in appropriate positions. Complete assignments of the signals in the ¹H, ¹³C, and ¹⁴N NMR spectra of the compounds obtained were carried out. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1595–1599, September, 2006.     

Quantitative 2H NMR spectroscopy. 1. Thermodynamic H/D isotope effects in N,N-dimethylformamide and cyclopentadiene molecules

A new method for quantification of the relative distribution of deuterium in molecules is proposed. The technique is based on the lineshape analysis in the ²H NMR spectra obtained at the natural abundance level of deuterium with allowance for inhomogeneity of the magnetic field. The equilibrium thermodynamic H/D isotope effects for hindered rotation about the C—N bond in the N,N-dimethylformamide molecule and for prototropic exchange in the cyclopentadiene molecule were determined. The results obtained agree with those of DFT calculations of the vibrational energies.     

Synthesis and anti-inflammatory activity of acetylsalicylamino acids and peptides

Several water-soluble acetylsalicylamino acids and peptides containing neutral and acidic amino acids were synthesized and investigated for anti-inflammatory activity. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 169–172, March–April, 2006.     

Synthesis of first nonannulated 1,2,3,4-tetrazine 1,3-dioxides

Thermolysis of o-diazidobenzotetrazine 1,3-dioxides was accompanied by cleavage of the C-C bond of the benzene ring to give nonannulated 1,2,3,4-tetrazine 1,3-dioxides. The structures of these first representatives of nonfused 1,2,3,4-tetrazines were confirmed by ¹³C and ¹⁴N NMR spectroscopy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1589–1594, September, 2006.     

Geminal systems. 50. Synthesis and alcoholysis of N-acyloxy-N-alkoxy derivatives of ureas,carbamates, and benzamides

Procedures were developed for the synthesis of N-acyloxy-N-alkoxy derivatives of ureas, carbamates, and benzamides by the reactions of the corresponding N-alkoxy-N-chloro derivatives with sodium carboxylates in MeCN. N-Chloro-N-ethoxy-p-toluenesulfonamide was inert in this reaction. Alcoholysis of N-acyloxy-N-alkoxy derivatives of ureas, carbamates, and tert-alkylamines afforded the corresponding N,N-dialkoxy derivatives, whereas alcoholysis of N-acetoxy-N-ethoxybenzamide gave rise to alkyl benzoates.     

Synthesis and structure of azomethines based onN-vinyl derivatives of 2-amino- and 2-formylimidazoles

New Schiff's bases of theN-vinylimidazole andN-vinylbenzimidazole series were synthesized.¹H NMR data suggest that the azomethines exist in theE-form with respect to the CH=N bond and that the vinyl groups havetrans-orientation relative to each other. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 1857–1859, October, 1997.     

Synthesis of phenyldithioglyoxalic acid and its esters. A route to a-ketodithioacid derivatives

A novel route has been developed for the direct synthesis of the hitherto unknowna-ketodithioacid. Benzaldehyde has been treated with carbon disulphide in the presence of potassium cyanide, thereby making the intermediate carbanion Ph-C(OH)CN to add on to carbon disulphide eventually leading to thea-ketodithioacid. The methyl and ω-carboxypropyl esters of this acid have also been prepared.     

N-substituted amides of 2-cyanopenta-2E,4-dienoic acid

N-Substituted amides of 2-cyanopenta-2E,4-dienoic acid were synthesized by condensation ofN-substituted cyanoacetamides with acrolein in a dioxane-DMSO solution in the presence of Zn(OAc)₂·2H₂O as a condensing agent. X-ray diffraction study of 3-methylanilide of 2-cyanopenta-2E,4-dienoic acid (2d) demonstrated that the crystal structure of this compound is similar to that of 2-cyanopenta-2E,4-dienoic acid studied previously. However, the presence of themeta-tolyl substituent in molecule2d apparently results in the fact that the β-structure, which is typical of 2-cyanopenta-2E,4-dienoic acid, does not exist in the crystalline phase of2d. Henkel Kommanditgesellschaft auf aktien, Deutschland, D-40191 Dusseldorf, Henkelstrasse, 67. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 933–937, May, 1999.