Synthesis of pyrimidine 2'-deoxy ribonucleosides branched at the 2'-position via radical atom-transfer cyclization reaction with a vinylsilyl group as a radical-acceptor tether.
Recently, we developed a regio- and stereoselective method for introducing a vinyl group at the position beta to a hydroxyl group in halohydrins or alpha-phenylselenoalkanols via a radical atom-transfer cyclization reaction with a vinylsilyl group as a temporary connecting radical-acceptor tether. The synthesis of 2'-deoxy-2'-C-vinyl- and 2'-deoxy-2'-C-hydroxymethyluridines (7 and 8, respectively) and the corresponding 2'-deoxycytidine congeners (10 and 11, respectively), which were designed as potential antitumor and/or antiviral agents, was achieved using this radical atom-transfer cyclization as the key step. When the 2'-deoxy-2'-iodo-5'-O-monomethoxytrityl (MMTr) uridine derivative 19a, bearing a vinylsilyl group at the 3'-hydroxyl group, was heated with (Me(3)Sn)(2) and AIBN in benzene, the corresponding radical atom-transfer product was generated, which in turn was successively treated with tetrabutylammonium fluoride and TBSCl/imidazole to give the desired 2'-deoxy-5'-O-MMTr-3'-O-TBS-2'-C-vinyluridine (25). Compound 25 was successfully converted into the target 2'-deoxy-2'-branched pyrimidine ribonucleosides 7, 8, 10, and 11.
Sukeda
M
M
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Shuto
S
S
Sugimoto
I
I
Ichikawa
S
S
Matsuda
A
A
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D014753:Vinyl Compounds
D000970:Antineoplastic Agents; D003853:Deoxyribonucleosides; D005609:Free Radicals; D014753:Vinyl Compounds