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Synthesis of (±)-9-[c-4, t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (BCA) derivatives branched at the 4′-position based on intramolecular SH2′ cyclization |
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| Authors: | Hiroki Kumamoto Nonoko Takahashi Hiromichi Tanaka Takayuki Hamasaki Hiroshi Abe Nobuyuki Kato |
| Affiliation: | 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 c Nanomedical Engineering Laboratory, Discovery Research Institute, Riken, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan d Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan |
| Abstract: | Synthesis of 4′-branched BCA analogues (5) was carried out. Stereospecific construction of the cis-disposed 4′-carbon-substituents and 5′-hydroxymethyl group was secured by employing the bicyclo[3.3.0]lactone 16 as a key intermediate, which was prepared by radical-mediated intramolecular SH2′ cyclization of the phenylselenomethyl ester 15. After manipulation of the double bond of 16, bis(Boc)adenine was introduced based on the Mitsunobu reaction of the allyl alcohol 24. Transformation of the lactone function of 27 allowed preparation of the 4′-hydroxymethyl (31), the 4′-vinyl (32), the 4′-cyano (34), and the 4′-ethynyl (35) derivatives. Anti-HIV and anti-HCV activities of the free nucleosides 36-38 were also examined. |
| Keywords: | Carbocyclic nucleoside Radical cyclization Mitsunobu reaction |
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