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.

doi:10.1021/acs.oprd.6b00420

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.

Authors

A. Harsanyi

A. Conte

L. Pichon

A. Rabion

S. Grenier

G. Sandford

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

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