Synthesis of cyclopentanyl carbocyclic 5-fluorocytosine ((-)-5-fluorocarbodine) using a facially selective hydrogenation approach

J Org Chem. 2013 Jan 18;78(2):723-7. doi: 10.1021/jo302038d. Epub 2012 Dec 26.

Abstract

An efficient synthetic route to biologically relevant (-)-5-fluorocarbodine 6 was developed. Direct coupling of N(6)-protected 5-fluorouracil 15 with cyclopentenyl intermediate 13, followed by formation of a macrocycle between the base and the carbocyclic sugar moiety, via ring-closing metathesis, allowed for a facial selective hydrogenation of the sugar double bond to give, exclusively, the desired 4'-β stereoisomer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cyclization
  • Cyclopentanes / chemistry*
  • Cytidine / analogs & derivatives*
  • Cytidine / chemical synthesis
  • Cytidine / chemistry
  • Flucytosine / chemical synthesis*
  • Flucytosine / chemistry
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / chemical synthesis*
  • Fluorouracil / chemistry
  • Hydrogenation
  • Molecular Structure
  • Stereoisomerism

Substances

  • Cyclopentanes
  • Cytidine
  • carbodine
  • Flucytosine
  • Fluorouracil