Abstract
Continuous flow chemistry is by now an established and valued synthesis technology regularly exploited in academic and industrial laboratories to bring about the improved preparation of a variety of molecular structures. Benefits such as better heat and mass transfer, improved process control and safety, a small equipment footprint, as well as the ability to integrate in-line analysis and purification tools into telescoped sequences are often cited when comparing flow to analogous batch processes. In this short review, the latest developments regarding the exploitation of continuous flow protocols towards the synthesis of anticancer drugs are evaluated. Our efforts focus predominately on the period of 2016–2021 and highlight key case studies where either the final active pharmaceutical ingredient (API) or its building blocks were produced continuously. It is hoped that this manuscript will serve as a useful synopsis showcasing the impact of continuous flow chemistry towards the generation of important anticancer drugs.
Highlights
Drug shortages remain a significant public health issue in the 21st century
Flow chemistry has played a major part in developing effective syntheses of anticancer drugs
This has been demonstrated for the telescoped flow synthesis of anticancer drugs by academic as well as industrial laboratories to either generate proofof-concept case studies or for the preparation of multigram quantities of these anticancer drugs and their building blocks in a short time
Summary
Drug shortages remain a significant public health issue in the 21st century. All types of drugs are affected by this problem such as anticancer medicines, antimicrobial drugs, analgesics, opioids, cardiovascular drugs, radiopharmaceuticals, and parenteral products. It is of utmost importance to avoid shortages of medicines to ensure patients have the highest survival rate possible Both FDA (Food and Drug Administration) and EMA (European Medicines Agency) published updated reports analyzing this situation [4,5]. Drug shortages can occur for many reasons such as manufacturing and shipping problems or price changes and discontinuations of raw materials. Manufacturing issues occur because most pharmaceutical companies strongly rely on traditional batch processing and related supply networks. In this type of discontinuous processing, the raw material is processed in large vessels, in which the chemical reaction is allowed to proceed for a given period of time before the product is discharged and eventually purified (Figure 1). We wish to highlight the use of flow processes applied to the slpslpsaayyyrrssnnenettctcttffhhuhuiiveveerrsesssesioioisyssyrreesosooa..afffrrIIiiisnnsmmm((tt2p2pphh00oooii11ssrrr66tttrraa–a–eenn2n2vvt0t0tii2e2eaaa1w1wnnn))ttt.,.,iiicccwwaaaneenncccwweeerrriissdddhhrrruttuuoogggshshs iiaaaggnnnhhdddlliiggttthhhhheeettiiirtrtrhhbbbeeuuuuuiiilllssdddeeiiinnnoogggff fbfblllolooowwcckkppssrraaoossccereresespsspeeoossrrttaaeeppddppwwlliieeiitdtdhhitit3nnooottttfhhhh2ee4ee blocks as reported within the last five years (2016–2021)
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