A sustainable, efficient, and potentially cost-effective approach to the antimalarial drug candidate MMV688533

Abstract

A 6-step synthesis of the antimalarial drug candidate MMV688533 is reported.

A focus on sustainable method development for greener synthesis

“…Overall, the synthesis of MMV688533 presented by Kavthe et al 10 demonstrates how environmentally orientated methods can translate to more sustainable synthesis. By developing a new synthetic route featuring Sonogashira couplings under aqueous micellar conditions: PMI, catalyst loading, step economy and yield could all be simultaneously improved.…”

“…Quantitatively assessing the production of waste in both syntheses found that the process mass intensity (PMI) of the newly reported route (111 kg input per kg product) is less than half of what was calculated for the discovery route (287 kg input per kg product), highlighting the level of improvement in sustainability that this work has achieved. 14 Overall, the synthesis of MMV688533 presented by Kavthe et al 10 demonstrates how environmentally orientated methods can translate to more sustainable synthesis. By developing a new synthetic route featuring Sonogashira couplings under aqueous micellar conditions: PMI, catalyst loading, step economy and yield could all be simultaneously improved.…”

“…In their most recent publication (Kavthe et al, https://doi.org/10.1039/ D3SC01699D), 10 the methods and principles described above were directly applied to the development of an alternative synthetic route to MMV688533 (Fig. 1B), a promising new single-dose malaria treatment with a high barrier to Plasmodium falciparum parasite resistance which is currently in the advanced stages of clinical evaluation.…”