Machines vs Malaria: A Flow-Based Preparation of the Drug Candidate OZ439

Lau, Shing-Hing; Galván, Alicia; Merchant, Rohan R.; Battilocchio, Claudio; Souto, José A.; Berry, Michael S.; Ley, Steven V.

doi:10.1021/acs.orglett.5b01307

Cited by 52 publications

(20 citation statements)

References 34 publications

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“…Ley and co‐workers produced the desired trioxolanes, which are stable and act as precursors of a drug candidate for malaria, in 70 % of yield and a throughput of 1.9 g per hour. As shown in Scheme , a solution containing the oxime and the ketone was introduced in EtOAc in one feed and reacted with a stream of ozone …”

Section: ‐Membered Ringsmentioning

confidence: 99%

Flow Chemistry for Cycloaddition Reactions

2020

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Continuous flow reactors form part of a rapidly growing research area that has changed the way synthetic chemistry is performed not only in academia but also at the industrial level. This Review highlights the most recent advances in cycloaddition reactions performed in flow systems. Cycloadditions are atom-efficient transformations for the synthesis of carbo-and heterocycles, involved in the construction of challenging skeletons of complex molecules. The main advantages of translating these processes into flow include using intensified conditions, safer handling of hazardous reagents and gases, easy tuning of reaction conditions, and straightforward scaling up. These benefits are especially important in cycloadditions such as the copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), Diels-Alder reaction, ozonolysis and [2 + 2] photocycloadditions. Some of these transformations are key reactions in the industrial synthesis of pharmaceuticals.

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Section: ‐Membered Ringsmentioning

confidence: 99%

Flow Chemistry for Cycloaddition Reactions

2020

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“…Overcoming this issue was possible by dilution, while flow rate was increased in order to maintain the same level of throughput. 68 …”

Section: Ensuring Stability For Continuous Productionmentioning

confidence: 99%

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

Bana

Örkényi

Lövei

et al. 2017

Bioorganic & Medicinal Chemistry

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a b s t r a c tRecent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules.

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“…10% Pd/C, RT, 1 bar, 1.0 mL min −1 , 94% [41] Olefin reduction 10% Pd/C, 80°C, 60 bar, 2.0 mL min −1 , 90% [42] De-aromatisation 10% Ru/C or 10% Rh/C, 75-100°C, 50 bar, 1.0 mL min −1 , 100% [43] Selective reduction 20% Pd/C, 100°C, 5 bar, 1.0 mL min − In the synthesis of the antimalarial drug, OZ439 49, Lau et al optimised the hydrogenation step successfully reducing only one of the aromatic rings using 20% Pd/C (Figure 16) [44]. The concentration of the undesired minor by-products 50 and 51 was minimised by control of the temperature and the amount of hydrogen entering the system.…”

Section: Type Of Reaction Starting Materials Product Conditions Referementioning

confidence: 99%

Recent Developments in the Use of Flow Hydrogenation in the Field of Medicinal Chemistry

Russell¹,

Baker²,

Cossar³

et al. 2017

New Advances in Hydrogenation Processes - Fundamentals and Applications

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This chapter focuses on recent applications of flow hydrogenation in medicinal chemistry. Flow reactors can enhance laboratory safety, reducing the risks associated with pyrophoric catalysts, due to their containment in catalyst cartridges or omnifit columns. Flow hydrogenation reduces the risks arising from hydrogen gas, with either hydrogen generated in situ from water, or precise management of the gas flow rate through tube-in-tube reactors. There is an increasing body of evidence that flow hydrogenation enhances reduction outcomes across nitro, imine, nitrile, amide, azide, and azo reductions, together with de-aromatisation and hydrodehalogenation. In addition, olefin, alkyne, carbonyl, and benzyl reductions have been widely examined. Further, protocols involving multistage flow reactions involving hydrogenation are highlighted.

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Machines vs Malaria: A Flow-Based Preparation of the Drug Candidate OZ439

Cited by 52 publications

References 34 publications

Flow Chemistry for Cycloaddition Reactions

Flow Chemistry for Cycloaddition Reactions

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

Recent Developments in the Use of Flow Hydrogenation in the Field of Medicinal Chemistry

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