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An improved synthesis of adefovir and related analogues
An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444443/ https://www.ncbi.nlm.nih.gov/pubmed/30992729 http://dx.doi.org/10.3762/bjoc.15.77 |
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author | Jones, David J O’Leary, Eileen M O’Sullivan, Timothy P |
author_facet | Jones, David J O’Leary, Eileen M O’Sullivan, Timothy P |
author_sort | Jones, David J |
collection | PubMed |
description | An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach. |
format | Online Article Text |
id | pubmed-6444443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-64444432019-04-16 An improved synthesis of adefovir and related analogues Jones, David J O’Leary, Eileen M O’Sullivan, Timothy P Beilstein J Org Chem Full Research Paper An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach. Beilstein-Institut 2019-03-29 /pmc/articles/PMC6444443/ /pubmed/30992729 http://dx.doi.org/10.3762/bjoc.15.77 Text en Copyright © 2019, Jones et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms) |
spellingShingle | Full Research Paper Jones, David J O’Leary, Eileen M O’Sullivan, Timothy P An improved synthesis of adefovir and related analogues |
title | An improved synthesis of adefovir and related analogues |
title_full | An improved synthesis of adefovir and related analogues |
title_fullStr | An improved synthesis of adefovir and related analogues |
title_full_unstemmed | An improved synthesis of adefovir and related analogues |
title_short | An improved synthesis of adefovir and related analogues |
title_sort | improved synthesis of adefovir and related analogues |
topic | Full Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444443/ https://www.ncbi.nlm.nih.gov/pubmed/30992729 http://dx.doi.org/10.3762/bjoc.15.77 |
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