Unit

UNIT 14.2 Synthesis of Acyclic Nucleoside Phosphonates

  1. Antonin Holý

Published Online: 1 OCT 2005

DOI: 10.1002/0471142700.nc1402s22

Current Protocols in Nucleic Acid Chemistry

Current Protocols in Nucleic Acid Chemistry

How to Cite

Holý, A. 2005. Synthesis of Acyclic Nucleoside Phosphonates. Current Protocols in Nucleic Acid Chemistry. 22:14.2:14.2.1–14.2.38.

Author Information

  1. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Publication History

  1. Published Online: 1 OCT 2005
  2. Published Print: SEP 2005

Abstract

Acyclic nucleoside phosphonates (ANPs) are important biologically active nucleotide analogs. They contain an isopolar phosphonomethyl function linked to the hydroxyl group of an acyclic side-chain via an undegradable ether group. Though their most important activity is antiviral, some exhibit cytostatic or antiprotozoic effects. The three most important groups of ANP are presented here as synthetic procedures for a large laboratory scale. Synthesis follows three principles: (1) introduction of a protected phosphonomethyl group to the hydroxyl on an appropriate alkyl side-chain of an acyclic nucleoside, (2) alkylation of the heterocyclic base by a synthon with all characteristic features of the future phoshonate-bearing side-chain, or (3) transformation of a reactive group at the heterocyclic base. The last step in all these cases is removal of the phosphonate esters. Preparation methods are described in detail for PMEA, PMEG, PMEDAP and its N6-cyclopropyl derivative, (R)-PMPA, and (S)-HPMPA, as well as all intermediates and synthons.

Keywords:

  • Acyclic nucleoside phosphonates;
  • purine nucleotide analogs;
  • tenofovir;
  • adefovir;
  • antiviral