The modular Asia flow chemistry system from Syrris proved key to the success of a recently described process for accelerated total synthesis of spirodienal A and spirangien A methyl ester. Developed by the Ley Group at the Department of Chemistry, University of Cambridge, UK – and recently published in Angewandte Chemie International Edition¹ – the groundbreaking work describes the use of powerful flow chemistry techniques for complex multi-stage synthesis of spirocyclic polyketides.
A major advantage of the Asia system is the accuracy of its pumps at low flow rates.”
The flexible Asia system was crucial to the success of the study, offering a variety of flow techniques – including gas-liquid and solid phase chemistries, liquid-liquid extraction and continuous work-up – to enable faster reaction optimization and telescoping of reaction steps. Researchers benefitted from the Asia Pump’s capacity to smoothly handle low boiling point solvents, as well as rapid mixing and continuous work-up in glass microreactors with the advanced Asia FLLEX (Flow Liquid Liquid Extraction).
A major advantage of the Asia system is the accuracy of its pumps at low flow rates – as low as 1 µL/min – which allows us to perform flow reactions on milligram quantities of material, and the flexibility to change syringes enables anything from very small scale to large scale synthesis to be achieved. It is very easy to exclude water from the system, allowing organometallic reactions to be set up more rapidly.”
“The pressurized inlet for the pumps is also extremely useful for these reactions – pumping organometallic compounds can be problematic in flow chemistry giving us the confidence to try things that we would not previously have attempted and helping to reduce failure rates.”
This set-up allowed synthesis of essential, complex coupling fragments using newly developed flow chemistry methods for automated reagent addition, silylation, crotylation, ozonolysis, olefination, and oxidation, allowing these vital building blocks to be produced faster and more safely, with higher yields compared to batch reactions.
Newton, S., Carter, C. F., Pearson, C. M., de C. Alves, L., Lange, H., Thansandote, P. and Ley, S. V. (2014), Accelerating Spirocyclic Polyketide Synthesis using Flow Chemistry. Angew. Chem. Int. Ed., 53: 4915–4920.