A. A. Tumashov

Kinetic resolution of racemic 2-methyl-1,2,3,4-tetrahydroquinoline and its structural analogs by using 2-arylpropionyl chlorides

Acylation of 2-methyl-1,2,3,4-tetrahydroquinoline and 2-methylindoline with the acyl chlorides of naproxen, ibuprofen, and 2-phenylpropionic acid has been found to lead to efficient kinetic resolution with predominant formation of the (S,S)-(R,R)-diastereoisomers. The highest acylation stereoselectivity was found in toluene at -20°C. No significant kinetic resolution of N-(sec-butyl)aniline and 2-methylpiperidine was achieved by using 2-arylpropionyl chlorides.

Specific features of heterocyclization of (E)-3-(2-ethoxyphenyl)-1-phenylprop-2-en-1-one with aminoazoles

A reaction of 3-(2-ethoxyphenyl)-substituted chalcone with aminoazoles was studied. The nature of aza groups in aminoazoles was found to affect the regioselectivity of β-amination in the course of the formation of isomeric pyrazolo[3,4-b]pyridine, azolo[1,5-a]- and [4,3-a]-pyrimidine systems and the depth of the reaction were determined. A regulatory role of catalysts and solvents in the direction of the cascade reactions was established. Mechanisms of the reactions were suggested. A significance of the alkoxy substituent in chalcone for stereoselective synthesis of Michael adducts, including 3-(2-ethoxyphenyl)-3-(7-(2-ethoxyphenyl)-5-phenyl-6,7-dihydroazolopyrimidin-6-yl)-1-phenylpropan-1-ones, was demonstrated. The structures of products synthesized were established by 1H and 13C NMR spectroscopy and X-ray diffraction analysis.

Synthesis of enantiomers of N-(2-aminopurin-6-yl)amino acids

Nonracemic N-(2-aminopurin-6-yl)-substituted amino acids were synthesized by nucleophilic substitution of chlorine atom in 2-acetamido-6-chloropurine upon treatment with amino acid tert-butyl esters and subsequent removal of protecting groups. Their enantiomeric composition was determined by HPLC on chiral stationary phases.

Lactam ring stability of stereoisomers of 4-amino-substituted pyroglutamic acids in acidic medium

The acid hydrolysis of the lactam ring of cis and trans stereoisomers of 4-(1-piperidyl)-, 4-dibenzylamino-, 4-[(methyl)(phenyl)amino]-, 4-phenylamino-, and 4-(4-methoxyphenyl)-aminopyroglutamic acids was studied. It was shown that the relative stability of the lactam ring of 4-amino-substituted pyroglutamic acids to acid hydrolysis depends both on the structure of a substituent in the position 4 and on the configuration of the compounds studied. Among these compounds, 4-amino-1-arylpyroglutamic acids were the most stable in acidic medium. The trans isomers are more stable than the corresponding cis isomers.

Mutual kinetic resolution of 3-methyl-3,4-dihydro-2 H -1,4-benzoxazines and 2-alkoxyacyl chlorides

Stereoselective acylation of racemic 3-methyl-3,4-dihydro-2Н-1,4-benzoxazine and its 7,8-difluoro-substituted analog with racemic 2-alkoxyacyl chlorides was stidied. The reactions of 3-methyl-3,4-dihydro-2H-1,4-benzoxazines with 2-methoxyisopentanoyl chloride were found to be more selective (selectivity factor s 31–32) compared to the acylation with other studied propanoyl chlorides (s 18–21). This fact was probably caused by the significant steric hindrance due to the isopropyl substituent in acyl chloride compared to the methyl group in reagents derived from propanoic acid.

Enantioselective microbial synthesis of ( S )-7,8-difluoro-3,4-dihydro-3-methyl-2 H -[1,4]benzoxazine

New strains of Rhodococcus erythropolis 25 and Microbacterium paraoxydans 20-11c actinobacteria were used to obtain (S)-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (99.6% ee) by enantioselective microbial hydrolysis of the corresponding racemic N-acetyl derivative.