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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2019-03-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.15.77 |
| _version_ | 1819169042688114688 |
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| author | David J. Jones Eileen M. O’Leary Timothy P. O’Sullivan |
| author_facet | David J. Jones Eileen M. O’Leary Timothy P. O’Sullivan |
| author_sort | David J. Jones |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T19:13:13Z |
| format | Article |
| id | doaj.art-c2aa1d66016741ac8a84ec48674a15b9 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-22T19:13:13Z |
| publishDate | 2019-03-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-c2aa1d66016741ac8a84ec48674a15b92022-12-21T18:15:37ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972019-03-0115180181010.3762/bjoc.15.771860-5397-15-77An improved synthesis of adefovir and related analoguesDavid J. Jones0Eileen M. O’Leary1Timothy P. O’Sullivan2School of Chemistry, University College Cork, Cork, IrelandDepartment of Physical Sciences, Cork Institute of Technology, Cork, IrelandSchool of Chemistry, University College Cork, Cork, IrelandAn 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.https://doi.org/10.3762/bjoc.15.77acyclic nucleoside phosphonateadefoviralkylationantiviralN-alkylationpurine |
| spellingShingle | David J. Jones Eileen M. O’Leary Timothy P. O’Sullivan An improved synthesis of adefovir and related analogues Beilstein Journal of Organic Chemistry acyclic nucleoside phosphonate adefovir alkylation antiviral N-alkylation purine |
| 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 | acyclic nucleoside phosphonate adefovir alkylation antiviral N-alkylation purine |
| url | https://doi.org/10.3762/bjoc.15.77 |
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