Synthesis of (±)-4′-ethynyl-5′,5′-difluoro-2′,3′-dehydro-3′-deoxy- carbocyclic thymidine: a difluoromethylidene analogue of promising anti-HIV agent Ed4T |
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| Authors: | Hiroki Kumamoto Kazuhiro Haraguchi Kazuo T Nakamura Takayuki Hamasaki Satoko Shimbara Matsubayashi |
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| Institution: | a School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
b Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan |
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| Abstract: | Synthesis of (±)-4′-ethynyl-5′,5′-difluoro-2′,3′-dehydro-3′-deoxy-carbocyclic-thymidine (8) was carried out. The difluoromethylylidene group of 8 was constructed by the electrophilic fluorination to the cyclopentenone 11 by using Selectfluor®. Introduction of thymine base was investigated based on the Mitsunobu reaction by employing cyclopentenyl allyl alcohols variously substituted at the 4-position. It was found the 4-methoxycarbonyl derivative 14 gave the highest selectivity both in terms of regio- and stereochemistry. |
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| Keywords: | Carbocyclic nucleoside d4T gem-Difluoromethylidene Mitsunobu reaction |
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