Continuous one-flow multi-step synthesis of active pharmaceutical ingredients

Bloemendal, Victor R. L. J.; Janssen, Mathilde A. C. H.; Hest, Jan C. M. van; Rutjes, Floris P. J. T.

doi:10.1039/d0re00087f

Cited by 75 publications

(43 citation statements)

References 61 publications

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“…1a). This experiment is an example of multistep flow reaction sequences [33][34][35] and shows convincingly how to handle hazardous intermediates. The explosion-sensitive diazonium salts are generated in the first step and immediately reacted away in an electrophilic substitution reaction [36,37].…”

Section: Experiments 1: Synthesis Of Solvent Yellow 7 In Continuous Flowmentioning

confidence: 80%

Flow chemistry experiments in the undergraduate teaching laboratory: synthesis of diazo dyes and disulfides

et al. 2020

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By embedding flow technology in the early phases of academic education, students are exposed to both the theoretical and practical aspects of this modern and widely-used technology. Herein, two laboratory flow experiments are described which have been carried out by first year undergraduate students at Eindhoven University of Technology. The experiments are designed to be relatively risk-free and they exploit widely available equipment and cheap capillary flow reactors. The experiments allow students to develop a hands-on understanding of continuous processing and gives them insights in both organic chemistry and chemical engineering. Furthermore, they learn about the benefits of microreactors, continuous processing, multistep reaction sequences and multiphase chemistry. Undoubtedly, such skills are highly valued in both academia and the chemical industry.

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Section: Experiments 1: Synthesis Of Solvent Yellow 7 In Continuous Flowmentioning

confidence: 80%

Flow chemistry experiments in the undergraduate teaching laboratory: synthesis of diazo dyes and disulfides

et al. 2020

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“…Also, more concern should be paid for the overall sustainability of the synthetic sequences including the renewability of the starting materials (Kühlborn et al, 2020). Furthermore, one-pot reactions, along with the preparation of substrates and post-functionalization, can be combined with flow chemistry and integrated into automatic syntheses (Jürjens et al, 2015;Coley et al, 2019;Bloemendal et al, 2020;Chatterjee et al, 2020;Nam et al, 2020), which should have new opportunities to further improvement of synthetic efficiency.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

Zheng

Hua

2020

Front. Chem.

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Polycyclic scaffolds are omnipresent in natural products and drugs, and the synthetic strategies and methods toward construction of these scaffolds are of particular importance. Compared to simple cyclic ring systems, polycyclic scaffolds have higher structure complexity and diversity, making them suitable for charting broader chemical space, yet bringing challenges for the syntheses. In this review, we surveyed progress in the past decade on synthetic methods for polycyclic natural product scaffolds, in which the key steps are one-pot reactions involving intermolecular or intramolecular alkyne annulation. Synthetic strategies of selected polycyclic carbocycles and heterocycles with at least three fused, bridged, or spiro rings are discussed with emphasis on the synthetic efficiency and product diversity. Recent examples containing newly developed synthetic concepts or toolkits such as collective and divergent total synthesis, gold catalysis, C-H functionalization, and dearomative cyclization are highlighted. Finally, several "privileged synthetic strategies" for "privileged polycyclic scaffolds" are summarized, with discussion of remained challenges and future perspectives.

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“…The preparation of APIs in a continuous flow process is desirable as it increases safety, scalability, reproducibility and efficiency. Multistep cascade reactions, which can be carried out in a single flow system (One-Flow) are particularly attractive for the synthesis of pharmaceutically active small molecules [9]. Within the framework of our EU FETOPEN ONE-FLOW project [10], in which cascade one-flow approaches are being developed for the synthesis of APIs, we aimed to implement this strategy for producing cannabinoids.…”

Section: Introductionmentioning

confidence: 99%

One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo- and heterogeneous Lewis acids

et al. 2021

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Continuous flow chemistry holds great potential for the production of biologically relevant molecules. Herein, we present an approach for the continuous synthesis of cannabidiol and tetrahydrocannabinol in a one-flow system. The designed route consists of a reaction cascade involving Friedel-Crafts alkylation, subsequent ring opening and cyclisation in up to 45% yield. The reactions were successfully performed using both hetero- and homogeneous Lewis acids in continuous flow and provide yields that are similar to comparable batch processes. Graphical abstract

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Continuous one-flow multi-step synthesis of active pharmaceutical ingredients

Abstract: This review highlights a selection of multistep continuous flow (one-flow) processes leading to the synthesis of active pharmaceutical ingredients (APIs).

Cited by 75 publications

References 61 publications

Flow chemistry experiments in the undergraduate teaching laboratory: synthesis of diazo dyes and disulfides

Flow chemistry experiments in the undergraduate teaching laboratory: synthesis of diazo dyes and disulfides

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation

One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo- and heterogeneous Lewis acids

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