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An illustrative alternative example for the application of expert knowledge to tackle a roadblocking problem is the flow synthesis of artemisinin (Figure 1.11), developed by Peter Seeberger and coworker [72]. The discovery of artemisinin is a thrilling story of its own, which has been reviewed several times [73]. It is an essential drug for treatment of malaria, a devastating disease with a significant disease burden. It is estimated that every year 300 million children are infected with malaria. As this trypanosomal disease is widespread in developing countries, the production cost is a significant point to consider. Furthermore, the short half‐life of the drug requires relatively high doses for successful treatment. Artemisinin has a challenging molecular structure, characterized by a complex molecular framework. The complex sesquiterpene endoperoxide is deemed too complex to be accessible by total synthesis in required quantities.

Figure 1.11 Seeberger's flow synthesis of artemisinin and artemether, essential drugs for treatment of malaria.

Source: Based on Levesque and Seeberger [72].

The Seeberger group used their knowledge of flow chemistry to design and optimize a flow process for the structurally related drug artemether [74] (Figure 1.11), utilizing in situ generated singlet oxygen for generation of a peroxide, followed by Hock cleavage. While this flow chemistry process was not implemented in the ultimate production process, which involves photooxidation of activated dihydroartemisinic acid and is capable of delivering average quantities of 370 kg per batch [75], the methodology still has great potential for future applications. In particular, it could be demonstrated on an impressive example that facile photochemistry can be applied in process chemistry by rethinking the production process and converting the synthesis from large‐scale bulk synthesis to steady small‐scale synthesis by using a continuous process, which also is capable of delivering large quantities of drug substance.