Flow chemistry

Flow chemistry is the development and study of chemical reactions whereby reactants are combined by pumping fluids, including solutions of reagents, through tubes at known rates. The relative proportions of the reactants are controlled by their concentrations and relative flow rates. These reactions can take advantage of rapid mixing and surface to volume ratio effects.

Latest Research and Reviews

  • Research
    | Open Access

    PMOs (phosphorodiamidate morpholino oligomers) have huge potential for antisense therapy but complex and slow synthesis limits application. Here, the authors report the development of automated flow synthesis methods which reduce nucleobase coupling times from hours to minutes removing human errors and allow for high-throughput production.

    • Chengxi Li
    • , Alex J. Callahan
    •  & Bradley L. Pentelute
  • Research |

    Although strategies for the automated assembly of compounds of pharmaceutical relevance is a growing field of research, the synthesis of small-molecule pharmacophores remains a predominantly manual process. Now, an automated six-step synthesis of prexasertib is achieved by multistep solid-phase chemistry in a continuous-flow fashion using a chemical recipe file that enables automated scaffold modification through both early and late-stage diversification.

    • Chenguang Liu
    • , Jiaxun Xie
    •  & Jie Wu
    Nature Chemistry 13, 451-457
  • Research
    | Open Access

    Flow reactors have applications in reaction screening and optimisation, but typically operate in linear or radial configurations. Here a bench-top parallel flow synthesiser which distributes reagents between sixteen microreactors allows for rapid optimisation of chemical libraries, with uniform flow distribution even when clogging occurs.

    • Gwang-Noh Ahn
    • , Brijesh M. Sharma
    •  & Dong-Pyo Kim
  • Research
    | Open Access

    Translating discovery scale vial-based batch reactions to continuous flow scale-up conditions is limited by significant time and resource constraints. Here, the authors report a photochemical droplet microfluidic platform, which enables high throughput reaction discovery in flow to generate pharmaceutically relevant compound libraries.

    • Alexandra C. Sun
    • , Daniel J. Steyer
    •  & Corey R. J. Stephenson
  • Research |

    An automated synthesis instrument comprising a series of continuous flow modules that are radially arranged around a central switching station can achieve both linear and convergent syntheses.

    • Sourav Chatterjee
    • , Mara Guidi
    •  & Kerry Gilmore
    Nature 579, 379-384
  • Research |

    Tackling the loss of expensive cofactors is a key challenge in continuous-flow biocatalysis. This work reports immobilized enzymes with a tethered cofactor that is channelled between a recycling and a catalysis module facilitating total turnover numbers of NAD+ and ATP exceeding 10,000 in biocatalytic flow systems.

    • Carol J. Hartley
    • , Charlotte C. Williams
    •  & Colin Scott
    Nature Catalysis 2, 1006-1015

News and Comment

  • News & Views |

    Small-molecule drug discovery and development is limited by the ability of chemists to readily synthesize and purify new compounds with suitable chemical diversity. Now, a new twist on solid-phase chemical synthesis has enabled rapid and simplified synthesis of pharmaceutically relevant small molecules.

    • Mark S. Kerr
    •  & Kevin P. Cole
    Nature Chemistry 13, 399-401
  • News & Views |

    Fusion systems have been designed that link enzymes to cofactors and immobilization modules through appropriate synthetic spacers. These modular biocatalysts (assembling catalysis, cofactor provision/regeneration and assisted immobilization) are suited to heterogeneous biocatalysis systems and can be efficiently used in continuous flow reactors.

    • Martina Letizia Contente
    •  & Francesco Molinari
    Nature Catalysis 2, 951-952
  • Research Highlights |

    A rapid synthesis of the antibacterial drug linezolid using flow chemistry has been reported that does not require isolation or purification of any intermediates and is completed in seven synthetic steps

    • Stephen G. Davey
  • News & Views |

    Flow chemistry has grown in stature as a technique with the potential to deliver synthetic complexity with assembly-line-like efficiency. Application of flow technology to the front-line antimalarial drug artemisinin promises to revolutionalize treatment.

    • Kevin Booker-Milburn
    Nature Chemistry 4, 433-435