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

Harsanyi, A. and Conte, A. and Pichon, L. and Rabion, A. and Grenier, S. and Sandford, G. (2017) 'One-step continuous flow synthesis of anti-fungal WHO Essential Medicine Flucytosine using fluorine.', Organic process research & development., 21 (2). pp. 273-276.


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.

Item Type:Article
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Publisher statement:ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Date accepted:05 January 2017
Date deposited:16 January 2017
Date of first online publication:12 January 2017
Date first made open access:16 January 2017

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