Unit

UNIT 14.1 Synthesis of Acyclic Analogs of Adenosine

  1. Antonin Holý

Published Online: 1 OCT 2005

DOI: 10.1002/0471142700.nc1401s22

Current Protocols in Nucleic Acid Chemistry

Current Protocols in Nucleic Acid Chemistry

How to Cite

Holý, A. 2005. Synthesis of Acyclic Analogs of Adenosine. Current Protocols in Nucleic Acid Chemistry. 22:14.1:14.1.1–14.1.21.

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

This unit describes preparation of two groups of chiral acyclic nucleosides that are N-alkyl derivatives of adenine with hydroxyl group(s) on the alkyl chain. As an example of the neutral group, the synthesis is presented for (S)-(2,3,dihydroxypropyl)adenine (DHPA), a compound with multiple biological effects in proliferating systems. Its synthesis consists of alkylation of adenine with a suitable chiral synthon based on 1,2-O-isopropylideneglycerol. Another group of structurally related biologically active compounds are the 9-alkyladenines bearing both hydroxyl and carboxyl functions. Large-scale cyanohydrin reaction of the adenine-containing acetaldehyde intermediate yields 3-(adenin-9-yl)-2-hydroxypropanoic acid (AHPA). Lastly, one of the alternative syntheses of its homolog, the nucleoside antibiotic eritadenine (with a d-erythro-2,3-dihydroxybutanoic acid side-chain) is described starting from d-ribose. Procedures for preparation of all intermediates as well as the purification of the resulting crude material are described in detail. All these adenine derivatives inhibit SAM-dependent methylation reactions via inhibition of SAH hydrolase.

Keywords:

  • acyclic nucleoside analogs;
  • adenine derivatives;
  • methylation inhibitors;
  • DHPA;
  • AHPA;
  • eritadenine