Synthesis and Conformational Analysis of a Locked Analogue of Carbovir Built on a Bicyclo[3.1.0]-hex-2-enyl Template

Yongseok Choi, Guangyu Sun, Clifford George, Marc C. Nicklaus, James A. Kelley, Victor E. Marquez

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The synthesis and biological evaluation of a carbovir analogue (5) built on a bicyclo[3.1.0]hex-2-enyl template is described. A conformational analysis using density functional theory at the B3LYP/6-31G* level has been carried out on the rigid pseudosugar template of 5, the cyclopentene moiety of carbovir and the bicyclo[3.1.0]hex-2-yl pseudosugars of two isomeric carbonucleosides (12 and 13) containing exo- and endo-fused cyclopropane rings. The results show that while the planar configuration of the fused cyclopentane ring of compound 5 helps retain weak anti-HIV activity, the ability of the cyclopentene ring of carbovir to easily adopt a planar or puckered conformation with little energy penalty may prove to be a crucial advantage. The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13 that were inactive against HIV exhibited stiffer resistance to having a planar, fused cyclopentane moiety.

Original languageEnglish
Pages (from-to)2077-2091
Number of pages15
JournalNucleosides, Nucleotides and Nucleic Acids
Volume22
Issue number12
DOIs
Publication statusPublished - 2003

Keywords

  • Anti-HIV
  • Bicyclo[3.1.0]hex-2-enyl template
  • Carbocyclic nucleosides
  • Carbovir analogue
  • Conformationally locked

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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