A field guide to flow chemistry for synthetic organic chemists

Chemical Science, Journal Year: 2023, Volume and Issue: 14(16), P. 4230 - 4247

Published: Jan. 1, 2023

This review explores the benefits of flow chemistry and dispels notion that it is a mysterious “black box”, demonstrating how can push boundaries organic synthesis through understanding its governing principles.

Language: Английский

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Synthetic Molecular Photoelectrochemistry: New Frontiers in Synthetic Applications, Mechanistic Insights and Scalability

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(12)

Published: Sept. 3, 2021

Synthetic photoelectrochemistry (PEC) is receiving increasing attention as a new frontier for the generation and handling of reactive intermediates. PEC permits selective single-electron transfer (SET) reactions in much greener way broadens redox window possible transformations. Herein, most recent contributions are reviewed, demonstrating exciting opportunities, namely, combination with other reactivity paradigms (hydrogen-atom transfer, radical polar crossover, energy sensitization), scalability up to multigram scale, novel selectivities SET super-oxidations/reductions importance precomplexation temporally enable excited ion catalysis.

Language: Английский

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Advanced Real‐Time Process Analytics for Multistep Synthesis in Continuous Flow**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(15), P. 8139 - 8148

Published: Jan. 15, 2021

In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR UHPLC) synthesis active pharmaceutical ingredient, mesalazine. This synthetic route exploits processing for nitration, high temperature hydrolysis hydrogenation reactions, as well three inline separations. Advanced data analysis models were developed (indirect hard modeling, deep learning partial least squares regression), quantify desired products, intermediates impurities time, at multiple points along pathway. The capabilities system have been demonstrated by operating both steady state dynamic experiments represents step forward data-driven synthesis.

Language: Английский

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Bayesian Optimization of Computer-Proposed Multistep Synthetic Routes on an Automated Robotic Flow Platform

ACS Central Science, Journal Year: 2022, Volume and Issue: 8(6), P. 825 - 836

Published: June 10, 2022

Computer-aided synthesis planning (CASP) tools can propose retrosynthetic pathways and forward reaction conditions for the of organic compounds, but limited availability context-specific data currently necessitates experimental development to fully specify process details. We plan optimize a CASP-proposed human-refined multistep route toward an exemplary small molecule, sonidegib, on modular, robotic flow platform with integrated analytical technology (PAT) data-rich experimentation. Human insights address catalyst deactivation improve yield by strategic choices order addition. Multi-objective Bayesian optimization identifies optimal values categorical continuous variables in involving 3 reactions (including heterogeneous hydrogenation) 1 separation. The platform's modularity, reconfigurability, flexibility convergent are shown be essential allowing variation downstream residence time processes controlling addition minimize undesired reactivity. Overall, work demonstrates how automation, machine learning, robotics enhance manual experimentation through assistance idea generation, design, execution, optimization.

Language: Английский

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GreenMedChem: the challenge in the next decade toward eco-friendly compounds and processes in drug design

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(6), P. 2109 - 2169

Published: Jan. 1, 2023

Green chemistry has become a hot topic and the focus of not only many companies but also researchers.

Language: Английский

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Applications of machine learning in antibody discovery, process development, manufacturing and formulation: Current trends, challenges, and opportunities

Computers & Chemical Engineering, Journal Year: 2024, Volume and Issue: 182, P. 108585 - 108585

Published: Jan. 11, 2024

While machine learning (ML) has made significant contributions to the biopharmaceutical field, its applications are still in early stages terms of providing direct support for quality-by-design based development and manufacturing biologics, hindering enormous potential bioprocesses automation from their manufacturing. However, adoption ML-based models instead conventional multivariate data analysis methods is significantly increasing due accumulation large-scale production data. This trend primarily driven by real-time monitoring process variables quality attributes products through implementation advanced analytical technologies. Given complexity multidimensionality a bioproduct design, bioprocess development, product data, approaches increasingly being employed achieve accurate, flexible, high-performing predictive address problems analytics, monitoring, control within biopharma field. paper aims provide comprehensive review current ML solutions control, optimisation upstream, downstream, formulation processes monoclonal antibodies. Finally, this thoroughly discusses main challenges related themselves, use antibody Moreover, it offers further insights into innovative novel trends new digital solutions.

Language: Английский

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Pickering emulsion droplets and solid microspheres acting synergistically for continuous-flow cascade reactions

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(3), P. 295 - 306

Published: Feb. 13, 2024

Language: Английский

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Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates

Green Chemistry, Journal Year: 2021, Volume and Issue: 23(17), P. 6117 - 6138

Published: Jan. 1, 2021

Catalytic enantioselective transformations provide well-established and direct access to stereogenic synthons that are broadly distributed among active pharmaceutical ingredients (APIs). These reactions have been demonstrated benefit considerably from the merits of continuous processing microreactor technology. Over past few years, flow catalysis has grown into a mature field found diverse applications in asymmetric synthesis pharmaceutically substances. The present review therefore surveys chemistry-based approaches for chiral APIs their advanced intermediates, covering utilization biocatalysis, organometallic metal-free organocatalysis introduce asymmetry continuously operated systems. Single-step processes, interrupted multistep syntheses, combined batch/flow processes uninterrupted one-flow syntheses discussed herein.

Language: Английский

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Towards the Standardization of Flow Chemistry Protocols for Organic Reactions

Chemistry - Methods, Journal Year: 2021, Volume and Issue: 1(11), P. 454 - 467

Published: Sept. 13, 2021

Abstract Flow chemistry studies can sometimes be difficult to reproduce. In this article we provide guidance scientists for experimental details that should considered as part of any organic chemistry‐based continuous flow study. A focus is placed on information provided within reported enable experiments more easily and reliably reproduced. Topics covered include reactor components assembly, important parameter effects useful performance criteria. The covers aspects homogeneous systems, multiphase transformations, catalytic reactions (homogeneous heterogeneous). detailed discussion photochemistry, biocatalysis electrochemical systems outside the scope review.

Language: Английский

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Autonomous Multi‐Step and Multi‐Objective Optimization Facilitated by Real‐Time Process Analytics

Advanced Science, Journal Year: 2022, Volume and Issue: 9(10)

Published: Feb. 1, 2022

Autonomous flow reactors are becoming increasingly utilized in the synthesis of organic compounds, yet complexity chemical reactions and analytical methods remains limited. The development a modular platform which uses rapid NMR FTIR measurements, combined with chemometric modeling, is presented for efficient timely analysis reaction outcomes. This tested four variable single-step (nucleophilic aromatic substitution), to determine most effective optimization methodology. self-optimization approach minimal background knowledge proves provide optimal parameters within shortest operational time. chosen then applied seven two-step problem (imine formation cyclization), active pharmaceutical ingredient edaravone. Despite exponentially increased this problem, achieves excellent results relatively small number iterations, leading >95% solution yield intermediate up 5.42 kg L

Language: Английский

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