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<sup>1</sup>
Makoto Sukeda
Satoshi Shuto
Isamu Sugimoto
Satoshi Ichikawa
Akira Matsuda
10.1021/jo000967l.s001
https://acs.figshare.com/articles/journal_contribution/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_sup_1_sup_/3686427
Recently, 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‘-<i>C</i>-vinyl- and 2‘-deoxy-2‘-<i>C</i>-hydroxymethyluridines (<b>7</b> and <b>8</b>, respectively)
and the corresponding 2‘-deoxycytidine congeners (<b>10</b> and <b>11</b>, 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‘-<i>O</i>-monomethoxytrityl (MMTr) uridine
derivative <b>19a</b>, bearing a vinylsilyl group at the 3‘-hydroxyl group, was heated with (Me<sub>3</sub>Sn)<sub>2</sub> 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‘-<i>O</i>-MMTr-3‘-<i>O</i>-TBS-2‘-<i>C</i>-vinyluridine (<b>25</b>). Compound <b>25</b> was successfully converted into
the target 2‘-deoxy-2‘-branched pyrimidine ribonucleosides <b>7</b>, <b>8</b>, <b>10</b>, and <b>11</b>.
2000-12-02 00:00:00
vinylsilyl group
deoxy
MMTr
TBS
AIBN
cyclization
hydroxyl