New tool for the combinatorial toolbox

Colour-changing resin makes it easy to see amines being removed from solution. It is common practice in combinatorial chemistry to use chemicals bound to resins to remove unwanted reagents or by-products from the reaction mixture. An excess of expensive resin is required, however, and conventional techniques for monitoring completion of the reaction are inappropriate for large libraries of compounds.

’We wished to prepare dual-functional resins that act as both scavenger and integral sensor of the chemistry that is taking place’, comments Mark Bradley, professor of Combinatorial Chemistry at Southampton University, who led the team from Southampton, Merck Biosciences Inc, Pfizer Global R & D, and GlaxoSmithKline. They used a resin which is commonly employed to mop up excess amines from reaction mixtures and modified it by attaching a dye that changes colour from yellow to blue in the presence of amines. As the resin removes excess amine from solution, the colour changes from blue to yellow allowing an easy visual detection of when all the amine has been removed. The successful application of this ’self-indicating’ methylisocyanate resin in the synthesis of a library of high-purity ureas is demonstrated with a range of amine starting materials.

Jason Micklefield, reader in Chemical Biology at UMIST, UK, comments, ’the resin should facilitate process optimisation and product purification in numerous other parallel syntheses of large compound libraries.’

Caroline Evans