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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 Tether1
journal contribution
posted on 2000-12-02, 00:00 authored by Makoto Sukeda, Satoshi Shuto, Isamu Sugimoto, Satoshi Ichikawa, Akira MatsudaRecently, we developed a regio- and stereoselective method for introducing a vinyl group at the
position β to a hydroxyl group in halohydrins or α-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 (Me3Sn)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.