Drug Candidate for Leishmaniasis

 

 

Synthesis of DNDI-VL-2098: A Potential Preclinical Drug Candidate for the Treatment of Visceral Leishmaniasis

 

Abstract

 

 

 

A process suitable for kilogram-scale synthesis of (2R)-2-methyl-6-nitro-2-{[4-(trifluoromethoxy)phenoxy]methyl}-2,3-dihydroimidazo[2,1-b][1,3]oxazole (DNDI-VL-2098, 2), a preclinical drug candidate for the treatment of visceral leishmaniasis, is described. The four-step synthesis of the target compound involves the Sharpless asymmetric epoxidation of 2-methyl-2-propen-1-ol, 8. Identification of a suitable synthetic route using retrosynthetic analysis and development of a scalable process to access several kilograms of 2 are illustrated. The process was simplified by employing in situ synthesis of some intermediates, reducing safety hazards, and eliminating the need for column chromatography. The improved reactions were carried out on the kilogram scale to produce 2 in good yield, high optical purity, and high quality.

Keywords:

leishmaniasis;

safety hazards; scalable process;

Sharpless asymmetric epoxidation

 

 

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