Integrated multistep flow synthesis
This Thematic Series is inspired by the research on integrated multistep flow synthesis as proposed by the just started FET-OPEN ONE-FLOW project of EU.
The ONE-FLOW idea is to translate 'vertical hierarchy' of common multistep flow synthesis with its complex machinery (many serially connected reactors and separators; all being process controlled) into a self-organising 'horizontal hierarchy' of a compartmentalized flow reactor system - a biomimetic digital flow cascade machinery with just one reactor passage. Along those lines, this project aims to develop a digital flow cascade machinery which performs all the multiple reactions in one step, which includes inventing innovative catalytic cascades, and uplift that by enabling the best bio- and chemocatalysts working door by door.
- Full Research Paper
- Published 29 Nov 2017
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Figure 1: Natural indole containing molecules 1–7 of biological importance and synthetic auxin analogue 8 req...
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Scheme 1: Synthetic strategy towards desired indole product 8.
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Scheme 2: Initial flow reactor setup for the synthesis of intermediate 11.
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Scheme 3: Coflore ACR setup for the synthesis of intermediate 11.
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Scheme 4: Quenching and work-up of the reaction stream from the Coflore ACR for the synthesis intermediate 11....
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Figure 2: X-ray structure of intermediate 11, and reductive cyclisation products 12 and 14, assigned structur...
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Scheme 5: Stepwise reduction of intermediate 11 under hydrogenation conditions. * Indicates potential tautome...
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Scheme 6: Flow sequence for the construction of product 8.
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Scheme 7: Assembled process for flow synthesis of product 8 with yields and throughputs.
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- Review
- Published 20 Feb 2018
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Figure 1: Chemical structure of UDCA.
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Figure 2: Chemical structures of bile acids and salts.
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Figure 3: Comparison between Wolff–Kishner and Mozingo reduction. Notably the overall chemical reaction is th...
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Figure 4: Reaction catalysed by the 12α-HSDH; the 12-OH group of CA or UCA is oxidized yielding 12-oxo-CDCA o...
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Figure 5: Epimerization reaction catalysed by the 7α-HSDH and 7β-HSDH; the 7α-OH group of CA (R = OH) or CDCA...
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Figure 6: Overview of the chemoenzymatic process for the production of UDCA from CA: The oxidation, reduction...
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Figure 7: Schematic representation of the flow reactor for the continuous conversion of CDCA to UDCA [93].
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Figure 8: Chemoenzymatic pathways for the formation of UDCA from CA that profit by the C7 hydroxylation activ...
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- Full Research Paper
- Published 23 Feb 2018
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Figure 1: Examples of naturally occurring oxazoles (a); some drugs containing oxazole as the active moiety (b...
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Scheme 1: Synthesis of oxazoles 4 by addition of acyl chlorides to azirines 2, as described by Hassner et al. ...
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Scheme 2: Preparation of 2-functionalized oxazoles 7 from 2-(chloromethyl)oxazoles 6 and their application to...
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Scheme 3: Integrated continuous-flow synthesis of 2-(azidomethyl)oxazoles 7.
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Scheme 4: Side products generated during the reaction of azirine 2a with bromoacyl bromide at room temperatur...
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Figure 2: HPLC monitoring of the formation of 2-(azidomethyl)oxazole 7a.
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Figure 3: Continuous sequential thermolysis of vinyl azides 1 and ring expansion of azirines 2 with bromoacet...
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Figure 4: Continuous-flow three-step sequential synthesis of 2-(azidomethyl)oxazoles 7a–c from vinyl azides 1a...
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- Full Research Paper
- Published 08 Mar 2018
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Figure 1: Commercially available antimalarial drugs.
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Scheme 1: Current batch syntheses of the key intermediate 5-(ethyl(2-hydroxyethyl)amino)pentan-2-one (6).
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Scheme 2: Retrosynthetic strategy to hydroxychloroquine (1).
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Scheme 3: Schematic representation for continuous in-line extraction of 10.
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Scheme 4: Optimization of the flow process for the synthesis of 12.
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- Full Research Paper
- Published 19 Mar 2018
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Figure 1: Targeted integrated multistep synthesis of valsartan (1) and sacubitril (2).
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Scheme 1: Suzuki–Miyaura coupling of phenylboronic acid 3 with various bromoarenes 4a–e (a: R1 = H, R2 = CH3; ...
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Figure 2: Particle size distribution of Ce0.495Sn0.495Pd0.01O2–δ after size reduction via milling and separat...
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Figure 3: Optical microscope images of fresh aqueous dispersions, 0.05 wt %, of (a) Ce0.495Sn0.495Pd0.01O2–δ ...
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Figure 4: Photos of vessels containing cyclohexane-in-water emulsions stabilised by particles of Ce0.495Sn0.4...
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Figure 5: Optical microscopy images of cyclohexane-in-water emulsions of Figure 4 after one month for particle concen...
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Figure 6: (top) Mean emulsion droplet diameter after 30 min as a function of particle concentration for syste...
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Figure 7: Mean particle diameter in aqueous dispersions as a function of Ce0.495Sn0.495Pd0.01O2–δ concentrati...
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Figure 8: Variation of the zeta potential and pH value of aqueous dispersions of Ce0.495Sn0.495Pd0.01O2–δ par...
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Figure 9: (a) Appearance of octane-in-water emulsions with time at 0.05 wt % of Ce0.495Sn0.495Pd0.01O2–δ (lef...
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Figure 10: (a) Variation of droplet diameter with particle concentration for octane-in-water emulsions stabili...
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Figure 11: (a) Variation of droplet diameter with particle concentration for toluene-in-water emulsions stabil...
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- Letter
- Published 26 Mar 2018
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Scheme 1: Enzymatic reaction schemes for the selective oxidation of trans-hex-2-enol. A: Alcohol dehydrogenas...
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Figure 1: Michaelis–Menten kinetics of the PeAAOx-catalysed oxidation of trans-hex-2-enol. Conditions: 50 mM ...
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Figure 2: The influence of the residence time on the conversion of trans-hex-2-enol (red squares) to trans-2-...
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Figure 3: Increasing the PeAAOx turnover numbers (TN) by increasing the residence time. Conditions: 6 mL flow...
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- Review
- Published 29 Mar 2018
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Figure 1: Assembly of catalyst-functionalized amphiphilic block copolymers into polymer micelles and vesicles...
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Scheme 1: C–N bond formation under micellar catalyst conditions, no organic solvent involved. Adapted from re...
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Scheme 2: Suzuki−Miyaura couplings with, or without, ppm Pd. Conditions: ArI 0.5 mmol 3a, Ar’B(OH)2 (0.75–1.0...
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Figure 2: PQS (4a), PQS attached proline catalyst 4b. Adapted from reference [26]. Copyright 2012 American Chemic...
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Figure 3: 3a) Schematic representation of a Pickering emulsion with the enzyme in the water phase (i), or wit...
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Scheme 3: Cascade reaction with GOx and Myo. Adapted from reference [82].
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Figure 4: Cross-linked polymersomes with Cu(OTf)2 catalyst. Reprinted with permission from [15].
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Figure 5: Schematic representation of enzymatic polymerization in polymersomes. (A) CALB in the aqueous compa...
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Figure 6: Representation of DSN-G0. Reprinted with permission from [100].
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Figure 7: The multivalent esterase dendrimer 5 catalyzes the hydrolysis of 8-acyloxypyrene 1,3,6-trisulfonate...
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Figure 8: Conversion of 4-NP in five successive cycles of reduction, catalyzed by Au@citrate, Au@PEG and Au@P...
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- Review
- Published 26 Jul 2018
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Figure 1: Key features of different approaches for unified multistep synthesis platform.
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Figure 2: Schematic representation of a unified platform for the flow synthesis (P1–P14 pumps, PBR packed bed...
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Figure 3: Layout of a unified synthesis platform (including all the component) for multiple drug molecules (a...
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Figure 4: Layout for synthesis of 4 molecules on a single platform (approach 2).
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Scheme 1: The overall process for the synthesis of diphenhydramine hydrochloride.
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Figure 5: Approach 3 for a unified platform for multistep synthesis. M1–M9 = mixers, R1–R4 = tubular reactors...
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- Full Research Paper
- Published 24 Aug 2018
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Figure 1: Continuous-flow process to produce and react N-chloramines.
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Figure 2: Left: Laboratory scale CSTR developed by our group [8]. Right: 5-stage CSTR configuration using co-fee...
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Figure 3: Continuous-flow amide 18 formation using 1-stage CSTR. Blue squares: FeCl3 included; red circles: F...
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Scheme 1: Continuous-flow transfer hydrogenation of in situ generated imines.
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