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

J Org Chem. 2000 Dec 29;65(26):8988-96. doi: 10.1021/jo000967l.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Cyclization
  • Deoxyribonucleosides / chemical synthesis*
  • Deoxyribonucleosides / chemistry
  • Free Radicals / chemistry
  • Magnetic Resonance Spectroscopy
  • Stereoisomerism
  • Vinyl Compounds

Substances

  • Antineoplastic Agents
  • Deoxyribonucleosides
  • Free Radicals
  • Vinyl Compounds