UNIT 14.1 Synthesis of Acyclic Analogs of Adenosine
Published Online: 1 OCT 2005
Copyright © 2005 by John Wiley and Sons, Inc.
Lab Protocol Title
Current Protocols in Nucleic Acid Chemistry
How to Cite
Holý, A. 2005. Synthesis of Acyclic Analogs of Adenosine. Current Protocols in Nucleic Acid Chemistry. 14.1.1–14.1.21.
- Published Online: 1 OCT 2005
- Published Print: SEP 2005
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