Continuous flow synthesis of antimalarials: opportunities for distributed autonomous chemical manufacturing

Abstract

The concept of distributed manufacturing of chemicals is presented and discussed, with specific focus on the context of preparing molecules that can combat the development of geographically-localised resistant strains of infectious pathogens. Specifically we present the case of antimalarial compounds and demonstrate that the flow chemistry community have already designed both a machine capable of distrubuted chemical manufacturing and a module that would be capable of producing artemisin derivatives at the point of use.

Seasonal and Differential Sesquiterpene Accumulation in Artemisia annua Suggest Selection Based on Both Artemisinin and Dihydroartemisinic Acid may Increase Artemisinin in planta

“…However, more research is needed to determine the extent, and which stress may increase ART without compromising biomass yield. In the meanwhile, new different systems for the in vitro conversion of DHAA into ART or its antimalarial derivatives (e.g., artemether and artemotil) have been recently reviewed and reported encouraging yields of up to 65% (Lévesque and Seeberger, 2012 ; Howard et al, 2017 ).…”

Continuous Flow Organic Chemistry: Successes and Pitfalls at the Interface with Current Societal Challenges

“…Both are also listed as essential drugs by the WHO. Most of the research devoted to the continuous flow preparation of artemisinin and derivatives aimed at the development of efficient yet affordable processes, since most populations affected by malaria are located in developing areas of the world . The most relevant and recent examples related to artemisinin and derivatives are discussed in this section.…”

Distributed Biological Foundries for Global Health

“…The entire process occurs all in one place, as opposed to traditional drug production methods, where these steps in the pharmaceutical supply chain all occur at different locations where the active pharmaceutical ingredients (API) are made in one plant and the formulation into the dose form with the excipient elsewhere. Others have demonstrated the synthesis of antimalarials in a distributable continuous‐flow system in the field (Figure c) . Because of their relatively small size and fully integrated nature, these systems are field deployable for on‐demand pharmaceutical production, with the potential for use by the military and in developing countries, as they can manufacture drugs and biologics at point of need.…”