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A novel entecavir analogue constructing with a spiro[2.4]heptane core structure in the aglycon moiety: Its synthesis and evaluation for anti-hepatitis B virus activity |
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| Authors: | Hiroki Kumamoto Misato Fukano Shuhei Imoto Satoru Kohgo Yuki Odanaka Masayuki Amano |
| Institution: | 1. School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan;2. Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan;3. Cinical Research Center, National Center for Global Health and Medicine, Tokyo, Japan;4. Departments of Infectious Diseases and Hematology, Kumamoto University School of Medicine, Kumamoto, Japan |
| Abstract: | Synthesis of a novel 2′-deoxy-guanine carbocyclic nucleoside 4 constructed with spiro2.4]heptane core structure in the aglycon moiety was carried out. Radical-mediated 5-exo-dig mode cyclization and following cyclopropanation proceeded efficiently to furnish the spiro alcohol 10. Subsequent Mitsunobu-type glycosylation between 13 and 14, deoxygenation of the 2′-hydroxyl group of 16 and deprotection of 17 gave the title compound 4. Compound 4 demonstrated moderate anti-HBV activity (EC50 value of 0.12 ± 0.02 µM) and no cytotoxicity against HepG2 cells was observed up to 100 µM. |
| Keywords: | Anti-HBV carbocyclic nucleoside entecavir spiro[2 4]heptane radical-mediated cyclization |