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

作者：Kumamoto Hiroki^*; Fukano Misato; Imoto Shuhei; Kohgo Satoru; Odanaka Yuki; Amano Masayuki; Kuwata Higashi Nobuyo; Mitsuya Hiroaki; Haraguchi Kazuhiro; Fukuhara Kiyoshi

来源：Nucleosides Nucleotides & Nucleic Acids, 2017, 36(7): 463-473.

DOI：10.1080/15257770.2017.1322209

• Anti-HBV
• carbocyclic nucleoside
• entecavir
• spiro[2
• 4]heptane
• radical-mediated cyclization

Synthesis of a novel 2-deoxy-guanine carbocyclic nucleoside 4 constructed with spiro[2.4]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 mu M) and no cytotoxicity against HepG2 cells was observed up to 100 mu M.

• 出版日期2017
• 单位NIH