One-step continuous flow synthesis of anti-fungal WHO Essential Medicine Flucytosine using fluorine

Harsanyi, A.; Conte, A.; Pichon, L.; Rabion, A.; Grenier, S.; Sandford, G.

Abstract

In Africa around 625 000 mortalities per annum (20% of HIV/AIDS related deaths) are due to the affects of the Cryptococcal meningitis (CM) fungal infection. Recently, the World Health Organisation (WHO) and the Infectious Disease Society of America (IDSA) recommended that the first line treatment for CM is a combination of amphotericin B and flucytosine, both now WHO Essential Medicines. However, flucytosine is not even registered for use in any African nation due, in part, to its relatively high cost of manufacture and lack of generic manufacturers. Currently, flucytosine is manufactured by an expensive four-step manufacturing process. Here we report a one-step continuous flow process involving the reaction of inexpensive cytosine with fluorine gas using stainless steel tubular laboratory and pilot-scale silicon carbide reactor devices which is readily scaleable to a manufacturing process with a low initial capital expenditure.

Citation

Harsanyi, A., Conte, A., Pichon, L., Rabion, A., Grenier, S., & Sandford, G. (2017). One-step continuous flow synthesis of anti-fungal WHO Essential Medicine Flucytosine using fluorine. Organic Process Research and Development, 21(2), 273-276. https://doi.org/10.1021/acs.oprd.6b00420

• Journal Article Type: Article
• Acceptance Date: Jan 5, 2017
• Online Publication Date: Jan 12, 2017
• Publication Date: Feb 17, 2017
• Deposit Date: Jan 12, 2017
• Publicly Available Date: Jan 16, 2017
• Journal: Organic Process Research and Development
• Print ISSN: 1083-6160
• Electronic ISSN: 1520-586X
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Issue: 2
• Pages: 273-276
• DOI: https://doi.org/10.1021/acs.oprd.6b00420
• Public URL: https://durham-repository.worktribe.com/output/1388698