Novel methods and syntheses toward HIV/AIDS and tuberculosis pharmaceuticals

[chemical formula] Described herein is a novel Lewis acid catalyzed rearrangement-coupling of oxygen heterocycles and bis(diethylamino)chlorophosphine that provides direct formation of the phosphonomethyl ether functionality found in several important antiretroviral agents. A wide range of dioxolanes and 1,3-dioxanes may be employed, furnishing the desired products in good yield. The utility of this method is demonstrated in a novel synthesis of tenofovir, an antiretroviral drug used in the treatment of HIV/AIDS and hepatitis B. [chemical formula] We have proposed a novel synthesis toward bedaquiline, the latest pharmaceutical to be released in the market for the treatment of multi-drug resistant tuberculosis. The synthesis of the final epoxide intermediate of our route has been achieved on multi-gram scale, and the subject of future investigation will focus on the final epoxide opening reaction. Our proposed route uses readily available, inexpensive starting materials, and would afford bedaquiline in a convergent fashion requiring six steps.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2017

Author dc:creator

• Ocampo, Charles E. (Charles Edward)

Advisor dc:contributor.advisor

• Timothy F. Jamison.

• Chemistry.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/112441

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/112441