Synthesis and Biological Activity of the Nucleoside Analogs Based on Polyfluoroalkyl-Substituted 1,2,3-Triazoles

Abstract

This paper offers the results of a synthesis and study of cytotoxicity and the anti-Epstein-Barr virus (EBV) activity of new 2-deoxy-2-chloro-pyranosyl derivatives of 4-tosyl-5-trifluoromethyl-1,2,3-triazole obtained via the addition reaction of the corresponding 2-N-chlorotriazole to the double bond of 3,4,6-tri-O-acetyl-D-glucal. Nucleoside mimetics, derivatives of 4-tosyl-5-polyfluoroalkyl-1,2,3-triazoles containing fragments of 3-chloro-tetrahydrofuran, 3-chloro-tetrahydropyran, tetrahydropyran, dihydrofuran, dihydropyran, or acyclic substituents, were also studied. Evaluation of cytotoxicity (trypan blue and MTT methods) and anti-EBV activity (polymerase chain reaction (PCR) method) showed high selectivity indices for the compounds 4a, 4b, 5b, 6, and 8. A total of 15 novel compounds were examined in this study.

Regio‐ and Stereoselectivity in 1,3‐Dipolar Cycloadditions: Activation Strain Analyses for Reactions of Hydrazoic Acid with Substituted Alkenes

“…[1][2][3][4][5] These reactions constitute a versatile tool in organic synthesis, among others, because they can be used to form a wide range of compounds in only one experimental step. [12][13][14][15][16] For asymmetrical dipoles and dipolarophiles, a 1,4-or 1,5cycloadduct may be formed, depending on the electronic characteristics of the substituents in the dipole or in the dipolarophile (Scheme 1b). [12][13][14][15][16] For asymmetrical dipoles and dipolarophiles, a 1,4-or 1,5cycloadduct may be formed, depending on the electronic characteristics of the substituents in the dipole or in the dipolarophile (Scheme 1b).…”

The synthesis of bisphosphonate analogues of nucleotides – derivatives of (α-phenyl)(α-fluoro)methylenebisphosphonic acids

“…Аналоги нуклеозидов 6а, 6b, 9 по-лучены по методам, описанным ранее [10,12,13]. Для соединения 9 гидроксильные группы в поло-жении 2,3 фуранозного цикла были защищены вве-дением изопропенильного заместителя по извест-ной методике [14].…”

“…и пента-фторалкильного заместителя (синглеты при -109 и -84 м.д.). Ввиду наличия нескольких диастерео-меров в ЯМР 13 C спектрах соединений 10 и 11 наблюдаются несколько групп сигналов как для алифатических, так и для ароматических ядер уг-лерода. В ИК-спектрах валентные колебания P=O групп представлены интенсивными полосами по-глощения в области 1027-1035 см -1 .…”

Fluorinated Triazoles and Tetrazoles

“…Nucleoside mimetics, N 2 -substituted derivatives of 4-tosyl-5-polyfl uoroalkyl-1,2,3-triazoles containing fragments of 3-chlorotetrahydrofuran, 3-chloro-tetrahydropyran, tetrahydropyran, dihydrofuran, dihydropyran, or acyclic substituents, were also studied 182 -186 [ 162 ]. It was demonstrated that some among the studied compounds exhibit a pronounced anti-Epstein-Barr virus (EBV) activity.…”

“…Known publications were cited in [ 162 ] concerning the structures of 1,2,3-triazole analogs of nucleosides containing a polyfl uoroalkyl substituent in the heterocyclic core 179 -181 . Nucleoside mimetics, N 2 -substituted derivatives of 4-tosyl-5-polyfl uoroalkyl-1,2,3-triazoles containing fragments of 3-chlorotetrahydrofuran, 3-chloro-tetrahydropyran, tetrahydropyran, dihydrofuran, dihydropyran, or acyclic substituents, were also studied 182 -186 [ 162 ].…”