Unusual radical 6-endo cyclization to carbocyclic-ENA and elucidation of its solution conformation by 600 MHz NMR and ab initio calculations

Org Biomol Chem. 2008 Dec 21;6(24):4627-33. doi: 10.1039/b813870b. Epub 2008 Oct 27.


In our previous paper (J. Am. Chem. Soc., 2007, 129, 8362), we reported the synthesis of 7-Me-Carba-LNA and 8-Me-Carba-ENA thymidine through 5-hexenyl or 6-heptenyl radical cyclization. Both 5-hexenyl and 6-heptenyl radical cyclized exclusively in the exo form, giving unwanted exocyclic C7-methyl group. In the present study, we showed that the regioselectivity of the 5-hexenyl radical cyclization could be favorably tuned by introduction of a hydroxyl group to the olefinic double bond, yielding about 9% of the 6-endo cyclization product. Possible pathways to give 6-endo cyclization product 9 compared to the intermediates responsible to give the 5-exo cyclization product 5 has been discussed. Based on this unique 6-endo cyclization strategy, a carbocyclic ENA modified thymidine (carba-ENA) has been successfully synthesized, which also enabled us to perform its full solution conformation analysis by using NMR (1H at 600 MHz) observables for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry
  • Cyclization
  • Ethylenes / chemistry*
  • Free Radicals / chemistry
  • Magnetic Resonance Spectroscopy
  • Nucleic Acid Conformation
  • Nucleic Acids / chemistry*
  • Quantum Theory
  • Solutions
  • Thymine / chemistry


  • Alkenes
  • Ethylenes
  • Free Radicals
  • Nucleic Acids
  • Solutions
  • ethylene
  • 1-hexene
  • Thymine