Трифторометиловмісні 3,4-дигідропіримідин-2-они та їх конденсовані аналоги

• Дата: 2018
• Автори: Mel’nikov, S. V., Tkachuk, V. M., Sukach, V. A., Vovk, M. V.
• Формат: Стаття
• Мова: Ukrainian
• Опубліковано: National University of Pharmacy 2018
• Теми: 3; 4-dihydropyrimidones; CF3-containing derivatives; inter- and intramolecular cyclocondensations; Biginelly reaction; nucleophilic addition; anti-HIV agents; UDC 547.853 547.221 544.437; 4-дигидропиримидоны; CF3-содержащие производные; межмолекулярные и внутри- молекулярные циклоконденсации; реакция Биджинелли; нуклеофильное присоединение; анти-ВИЧ агенты; УДК 547.853 547.221 544.437; 4-дигідропіримідони; CF3-вмісні похідні; міжмолекулярні та внутрішньомолекулярні циклоконденсації; реакція Біджинеллі; нуклеофільне приєднання; анти-ВІЛ агенти
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/ophcj.18.946
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

The information related to the methods of the synthesis of 4- and 6-trifluoromethyl-3,4-dihydropyrimidine- 2-ones and their condensed analogs as potent molecular platforms for the synthesis of bioactive compounds has been analyzed and systematized. The role of inter- and intramolecular cyclocondensations of CF3-containing substrates, as well as nucleophilic addition to C=N bond as key steps for construction of 4-trifluorinated derivatives has been emphasized. The major part of this article is devoted to the construction of trifluoromethyldihydropirimidones of a high optical purity and their thioanalogs based on the condensation of the chiral ureas and thioureas. A special attention is paid to asymmetric reactions, which are used for the synthesis of chiral analogs of the anti-HIV drug Efavirenz. It has been noted that Biginelly reaction of the corresponding fluorinated ketoesters is the common way for obtaining 6-trifluoromethylpyrimidones. The method allows obtaining the target products in one stage although it has limitations due to the need to isolate intermediate cyclic products, which in the future should be subjected to dehydration. The effect of the catalyst nature on the course of Biginelly reaction of trifluoromethylated substrates has been analyzed. It has been shown that nucleophilic 3,6-addition to 4-CF3- dihydropyrimidones is effective method for the synthesis of dihydroorotic acid derivatives.