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RESEARCH PRODUCT
Di-tert-butyl Phosphonate Route to the Antiviral Drug Tenofovir
Dorota FerencJule-philipp DietzB. Frank GuptonTimothy F. JamisonTill Opatzsubject
adefovirTert butylActive ingredientTenofovir010405 organic chemistrymedicine.drug_classOrganic Chemistryoxymethyl phosphonates010402 general chemistry01 natural sciencesCombinatorial chemistryPhosphonateArticletenofovir0104 chemical scienceschemistry.chemical_compoundantiviralschemistryphosphitesmedicineAdefovirPhysical and Theoretical ChemistryAntiviral drugmedicine.drugdescription
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(OtBu)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).
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-02-01 | Organic Process Research & Development |