K 81 Krasnov, V. P. Nano-sized melphalan and sarcolysine drug delivery systems: synthesis and prospects of application [Electronic resource] / V. P. Krasnov, M. A. Korolyova, E. L. Vodovozova // Russian Chemical Reviews. - 2013. - Vol.82, №8. - С. 783-814. - Bibliogr. : p. 811-814 (196 ref.) Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): SARCOLYSINE -- SYNTHESIS -- NANO-SIZED Аннотация: The results of experimental studies concerned with the development of nano-sized drug delivery systems for the antitumour drugs sarcolysine and melphalan are generalized. The structures and biological activities of nanocarriers in comparison with unmodified drugs are discussed. Particular attention is given to the liposomes containing lipid derivatives of sarcolysine and melphalan in the lipid bilayer \\\\expert2\\NBO\\Russian Chemical Reviews\\2013, V.82, N8, p.783.pdf |
K 46 Kinetic resolution of racemic 6-substituted 1,2,3,4-tetrahydroquinaldines with chiral acyl chlorides. Experiment and quantum chemical simulation / E. N. Chulakov, M. A. Korolyova, L. S. Sadretdinova [et al.] // Russian chemical bulletin. - 2021. - Vol. 70, № 5. - P890-899 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: A comparative study of the kinetic resolution (KR) of racemic 6-substituted 2-methyl-1,2,3,4-tetrahydroquinolines with acyl chlorides of (S)-naproxen, N-phthaloyl-(S)-leucine, and (R)-O-phenyllactic acid was carried out. The selectivity factors in the KR of racemic amines with acyl chlorides of (S)-naproxen and (R)-O-phenyllactic acid were shown to be approximately the same and higher than those for the KR of N-phthaloyl-(S)-leucyl chloride. The reasons for the stereodifferentiation in the KR of racemic tetrahydroquinaldines containing groups of different electronic properties by acyl chlorides of three different chiral acids were explained using the DFT method. The conditions for stabilizing π—π interactions of aromatic fragments of the reagents, which do not occur in the same form in the transition state and lead to the minor diastereoisomeric product, are created in the transition state of the faster acylation reaction with (S)-naproxen and (R)-O-phenyllactic acyl chlorides. In the case of the KR of 2-methyl-1,2,3,4-tetrahydroquinoline and 2-methyl-6-methoxy-1,2,3,4-tetrahydroquinoline with N-phthaloyl-(S)-leucyl chloride, the acylation diastereoselectivity is determined, most likely, by conformational factors. The individual (S)-enantiomer of 2-methyl-6-methoxy-1,2,3,4-tetrahydroquinoline of high optical purity was synthesized using the KR of the racemate with (S)-naproxen acyl chloride. |
Acylative kinetic resolution of racemic methyl-substituted cyclic alkylamines with 2,5-dioxopyrrolidin-1-yl (R)-2-phenoxypropanoate / D. A. Gruzdev, S. A. Vakarov, M. A. Korolyova [et al.] // Organic & biomolecular chemistry. - 2022. - Vol. 20, № 4. - P862-869 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: The diastereoselective acylation of a number of racemic methyl-substituted cyclic alkylamines with active esters of 2-phenoxypropanoic acid was studied in detail. The ester of (R)-2-phenoxypropanoic acid and N-hydroxysuccinimide was found to be the most selective agent. The highest stereoselectivity was observed in the kinetic resolution of racemic 2-methylpiperidine in toluene at −40 °C (selectivity factor s = 73) with the predominant formation of (R,R)-amide (93.7% de). To explain the observed stereoselectivity, DFT modelling of the transition states in the reactions of the title acylating agent with 2-methylpiperidine and 2-methylpyrrolidine was performed. The calculated values were in good agreement with experimental data. It has been demonstrated that the acylation proceeds via a concerted mechanism, in which the addition of an amine occurs simultaneously with the elimination of the hydroxysuccinimide fragment. The high stereoselectivity of the (R,R)-amide formation is largely ensured by the lower steric hindrances in the transition states as compared to the formation of (R,S)-amide. |
Korolyova, M. A. Theoretical study of the stereoselectivity in the reaction of 4-haloglutamic acid derivatives with arylamines / M. A. Korolyova, A. Yu. Vigorov, V. P. Krasnov // Russian chemical bulletin. - 2022. - Vol. 71, № 6. - P1135-1142 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: Diastereoselective nucleophilic substitution reaction of halogen in dimethyl (2S,4RS)-4-bromo- and 4-iodo-N-phthaloylglutamates with arylamines was studied within the framework of the electron density functional theory. According to calculations, the stereoselectivity of the substitution reaction with respect to (2S,4S)-isomers of 4-arylamino derivatives is determined not only by the steric hindrances in the transition state leading to minor (2S,4R)-diastereomers, but also by the stabilization of the corresponding initial reagents complex due to stacking interactions of the aromatic fragments of reagents. |