A segmented flow platform for on-demand medicinal chemistry and compound synthesis in oscillating droplets

Hwang, Ye-Jin; Coley, Connor W.; Abolhasani, Milad; Marzinzik, Andreas L.; Koch, Guido; Spanka, Carsten; Lehmann, Hansjörg; Jensen, Klavs F.

doi:10.1039/c7cc03584e

Cited by 81 publications

(66 citation statements)

References 32 publications

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“…From a combination of 14 substrates, eight photosensitizers, four UV filters, two solvents, and two temperatures, four new reactions were discovered, including rearrangements, ring openings, and cycloadditions ( Figure 4B). More recently, Jensen reported a fully automated segmented oscillatory flow reactor for the study of different processes, screening a number of continuous and discrete variables within the same platform [79]. Here, each reaction droplet, instead of being pushed through the reactor, is oscillated back and forth in a short microchannel for the desired residence time, providing good mixing and reducing the reactor size.…”

Section: Automated Screening Platforms For Flow Photochemistrymentioning

confidence: 99%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

313

223

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Continuous-flow chemistry has recently attracted significant interest from chemists in both academia and industry working in different disciplines and from different backgrounds. Flow methods are now being used in reaction discovery/methodology, in scale-up and production, and for rapid screening and optimization. Photochemical processes are currently an important research field in the scientific community and the recent exploitation of flow methods for these methodologies has made clear the advantages of flow chemistry and its importance in modern chemistry and technology worldwide. This review highlights the most important features of continuous-flow technology applied to photochemical processes and provides a general perspective on this rapidly evolving research field. Microflow Technology and Photochemistry: A Perfect MatchThe use of light to promote chemical reactions has been exploited since the 18th century, but only recently a resurgence has been observed in synthetic organic chemistry, in particular due to the development of visible-light photoredox catalysis [1-5]. All transformations involving light (e.g., Figure 1A-D) must consider, besides classical chemical parameters (i.e., reaction conditions), the photophysical aspects of the sensitizer (see Glossary)/photocatalyst (when used), and the reactor design. The latter, although often neglected by chemists, is a critical aspect for the outcome of the studied chemical transformation. This includes, for example, the size, shape, and material of the reaction vessel, the characteristics and positioning of the light source(s), and heat-transfer properties, particularly when high-intensity lamps are used [6,7]. The engineering and technological aspects of photochemical processes are often at the basis of the irreproducibility and non-scalability of such transformations.According to the Beer-Lambert law, light transmittance decreases exponentially with the distance from the light source ( Figure 1F). For a standard batch reactor (diameter at least in the centimeter range), light intensity decreases considerably from the flask walls to the middle of the reaction mixture, resulting in slow reactions and nonhomogeneous irradiation of the reaction mixture. Performing photochemical reactions in microchannels (ID < 1 mm) allows a higher and more homogeneous photon flux, resulting in shorter reaction times and consequently less side-product formation due to over-irradiation, often observed in batch [8,9]. Another advantage of microflow chemistry, correlated with the large surface:volume ratio, is improved heat and mass transfer, with the possibility to perform mass-transfer-limited multiphasic reactions efficiently [10]. Reactive chemicals and intermediates can be handled more safely in flow than in batch, as no accumulation of dangerous components occurs within the confined reactor volume due to the continuous nature of the process. Together, these result in often faster, safer, and higher-yielding reactions, with the possibility to perform reactions under condition...

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Section: Automated Screening Platforms For Flow Photochemistrymentioning

confidence: 99%

Flow Photochemistry: Shine Some Light on Those Tubes!

Sambiagio

Noël

2020

Trends in Chemistry

313

223

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“…In another mode, controlled multistep synthesis can be carried out in a three-phase droplet reactor, where inert gas maintains uniform droplet spacing, which was shown in a five-stage quantum-dot synthesis [271]. An even more sophisticated system was invented for in-demand medicinal chemistry with the use of oscillating droplets for multistep synthesis allowing precise control of the reactor temperature and residence time for each step [269] (Figure 6a).…”

Section: Microfluidics In Flow Analysis and Flow Synthesismentioning

confidence: 99%

“…Examples of droplet-based flow systems developed for synthetic (a)[269] and analytical (b)[270] purposes: (a) schematic of the automated droplet-based medicinal chemistry platform[269]. PS-phase sensor; PD-photodetector.…”

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confidence: 99%

Flow Chemistry in Contemporary Chemical Sciences: A Real Variety of Its Applications

Trojanowicz

2020

Molecules

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Flow chemistry is an area of contemporary chemistry exploiting the hydrodynamic conditions of flowing liquids to provide particular environments for chemical reactions. These particular conditions of enhanced and strictly regulated transport of reagents, improved interface contacts, intensification of heat transfer, and safe operation with hazardous chemicals can be utilized in chemical synthesis, both for mechanization and automation of analytical procedures, and for the investigation of the kinetics of ultrafast reactions. Such methods are developed for more than half a century. In the field of chemical synthesis, they are used mostly in pharmaceutical chemistry for efficient syntheses of small amounts of active substances. In analytical chemistry, flow measuring systems are designed for environmental applications and industrial monitoring, as well as medical and pharmaceutical analysis, providing essential enhancement of the yield of analyses and precision of analytical determinations. The main concept of this review is to show the overlapping of development trends in the design of instrumentation and various ways of the utilization of specificity of chemical operations under flow conditions, especially for synthetic and analytical purposes, with a simultaneous presentation of the still rather limited correspondence between these two main areas of flow chemistry.

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“…11,23 Such reactants tend to perform systematically poorly in chemical reactions, resulting in a significant drift in logP between designed and produced arrays. 23 Several teams [24][25][26][27][28] have therefore developed highthroughput approaches for the optimisation of reactions within medicinal chemistry workflows.…”

Section: Integration Of Reaction Optimisation and Synthesismentioning

confidence: 99%

Streamlining bioactive molecular discovery through integration and automation

2018

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Article:Chow, S orcid.org/0000-0002-3600-0497, Liver, S and Nelson, AS orcid.org/0000-0003-3886-363X (2018) Streamlining bioactive molecular discovery through integration and automation. Nature Reviews Chemistry, 2 (8). AbstractThe discovery of bioactive small molecules is generally driven via iterative design-make-purifytest cycles. Automation is routinely harnessed at individual stages in order to increase the productivity of drug discovery. We describe recent progress to automate and integrate two or more adjacent stages within discovery workflows. The value of these integrated technologies is illustrated in the context of specific discovery case studies. We note that, to maximise impact on the productivity of discovery, each of the integrated stages would need to have both high and matched throughput. We also consider the longer-term goal of realising the fully autonomous discovery of bioactive small molecules through integration and automation of all stages of discovery.

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A segmented flow platform for on-demand medicinal chemistry and compound synthesis in oscillating droplets

Cited by 81 publications

References 32 publications

Flow Photochemistry: Shine Some Light on Those Tubes!

Flow Photochemistry: Shine Some Light on Those Tubes!

Flow Chemistry in Contemporary Chemical Sciences: A Real Variety of Its Applications

Streamlining bioactive molecular discovery through integration and automation

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