ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines

preprint
submitted on 25.02.2020 and posted on 26.02.2020 by Brenden Derstine, John W. Tomlin, Cheryl Peck, Jule-Phillip Dietz, Brenden Herrera, Flavio S. P. Cardoso, Dinesh J. Paymode, Andrew C. Yue, Anthony J. Arduengo III, Till Opatz, David R. Snead, Rodger W. Stringham, D. Tyler McQuade, B. Frank Gupton

Abstract: Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate and tenofovir alafenamide fumarate. Starting from acyclic precursor diaminomalononitrile 12, a four-step protocol to tenofovir 1 will allow for vertical integration for more manufacturers. The key transformation is a more convergent one step procedure from 6 as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium tert-butoxide (MTB) and significant solvent reduction by eliminating the need for an intermediate workup. With the costs of HIV/AIDS treatments remaining a barrier for those most in need, lowering the raw material/processing costs and increasing the security of supply can increase patient access.

Funding

This work was funded by the Bill and Melinda Gates Foundation

History

Email Address of Submitting Author

bfgupton@vcu.edu

Institution

Virginia Commonwealth University

Country

United States

ORCID For Submitting Author

0000-0002-9243-8813

Declaration of Conflict of Interest

no conflict of interest

Exports