Preparation of Pyrimidine Alkenyl Acyclic Nucleoside Phosphonoamidates

Curr Protoc Nucleic Acid Chem. 2018 Sep;74(1):e56. doi: 10.1002/cpnc.56. Epub 2018 Aug 13.

Abstract

This synthetic protocol describes two strategies for the preparation of pyrimidine alkenyl acyclic nucleoside phosphonoamidates (ANPs), including linear and trisubstituted alkenyl derivatives. For the first procedure, a bis-trimethylsilyl ester of the parent alkenyl ANPs is the key intermediate that reacts with the desired amino acid ester and aryl alcohol. For the second procedure, an allyl phosphonoamidate bearing the ProTide promoieties is the key synthon employed as olefin partner for a cross-metathesis reaction with an alkylated nucleobase. © 2018 by John Wiley & Sons, Inc.

Keywords: ProTide; acyclic nucleoside phosphonate; allylphosphonoamidate; antiviral; cross-metathesis; prodrug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemistry
  • Alkylation
  • Amides / chemistry
  • Amino Acids / chemistry
  • Chromatography, High Pressure Liquid
  • Cyclization
  • Esters
  • Nuclear Magnetic Resonance, Biomolecular
  • Organophosphonates / chemistry*
  • Phosphoric Acids / chemistry
  • Pyrimidine Nucleosides / chemistry*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Alcohols
  • Amides
  • Amino Acids
  • Esters
  • Organophosphonates
  • Phosphoric Acids
  • Pyrimidine Nucleosides
  • phosphoramidic acid