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Updated: Jun 22, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Di-tert-butyl Phosphonate Route to the Antiviral Drug Tenofovir
Jule-Philipp Dietz1, Dorota Ferenc1, Timothy F Jamison2
1Department of Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, Mainz 55128, Germany.
Abstract:
Di-tert-butyl oxymethyl phosphonates were investigated regarding their suitability for preparing the active pharmaceutical ingredient tenofovir (PMPA). First, an efficient and simple access to the crystalline di-tert-butyl(hydroxymethyl)phosphonate was developed. O-Mesylation gave high yields of the active phosphonomethylation reagent. For the synthesis of tenofovir, a two-step sequence was developed using Mg(OBu)2 as the base for the alkylation of (R)-9-(2-hydroxypropyl)adenine. Subsequent deprotection could be achieved with aqueous acids. (Di-tert-butoxyphosphoryl)methyl methanesulfonate showed to be the most efficient electrophile tested, affording PMPA in 72% yield on a 5 g scale. The developed protocol could also be applied for the preparation of the hepatitis B drug adefovir (64% yield/1 g scale).
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