An improved synthesis of adefovir and related analogues

Jones, David J.; O'Leary, Eileen M.; O'Sullivan, Timothy P.

An improved synthesis of adefovir and related analogues

dc.contributor.author	Jones, David J.
dc.contributor.author	O'Leary, Eileen M.
dc.contributor.author	O'Sullivan, Timothy P.
dc.date.accessioned	2019-05-03T10:50:31Z
dc.date.available	2019-05-03T10:50:31Z
dc.date.issued	2019-03-29
dc.date.updated	2019-05-02T14:53:29Z
dc.description.abstract	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.	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Jones, D. J., O’Leary, E. M. and O’Sullivan, T. P. (2019) An improved synthesis of adefovir and related analogues' Beilstein Journal of Organic Chemistry, 15, pp. 801–810. doi: 10.3762/bjoc.15.77	en
dc.identifier.doi	doi:10.3762/bjoc.15.77	en
dc.identifier.eissn	1860-5397
dc.identifier.endpage	810	en
dc.identifier.issn	1860-5397
dc.identifier.journaltitle	Beilstein Journal Of Organic Chemistry	en
dc.identifier.startpage	801	en
dc.identifier.uri	https://hdl.handle.net/10468/7851
dc.identifier.volume	15	en
dc.language.iso	en	en
dc.publisher	Beilstein-Institut	en
dc.relation.uri	https://www.beilstein-journals.org/bjoc/articles/15/77
dc.rights	© 2019 Jones et al.; licensee Beilstein-Institut. This is an Open Access article under the terms of the Creative Commons Attribution License (http://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)	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0	en
dc.subject	Acyclic nucleoside phosphonate	en
dc.subject	Adefovir	en
dc.subject	Alkylation	en
dc.subject	Antiviral	en
dc.subject	N-alkylation	en
dc.subject	Purine	en
dc.title	An improved synthesis of adefovir and related analogues	en
dc.type	Article (peer-reviewed)	en