Synthesis of 3'-substituted-2',3'-deoxy-2'-methylidenepyrimidine nucleosides.
2'-deoxy-2'-methylideneuridine derivative 9 was converted into 2',3'-didehydro-2',3'-dideoxy-2'-phenyl-selenomethyl derivative 16, which was treated with NCS and tert-butyl carbamate to afford 3'-amino derivative 18 via a [2,3]-sigmatropic rearrangement. Treatment of 9 with DAST gave a mixture of 2',3'-didehydro-2', 3'-dideoxy-2'-fluoromethyl derivative 19 and 3'-"up"-fluoro-2'-methylidene derivative 20 in a ratio of 1.5 : 1. On the other hand, when 12 was treated with DAST, 19 and 3'-"down"-fluoro-2'-methylidene derivative 21 were obtained in a ratio of 1 : 1.6. These nucleosides were converted into the corresponding cytidine derivatives 4, 6, and 8, respectively. The reaction mechanisms as well as biological activity of these compounds will also be discussed.
Hassan
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AA
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Matsuda
A
A
D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis*
D011741:Pyrimidine Nucleosides; D003841:Deoxycytidine; C056034:2'-deoxy-2'-methylenecytidine