Adventures in diversity-oriented synthesis

ORGN 410

David R. Spring, drspring@ch.cam.ac.uk, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom
The synthesis of structurally diverse and structurally complex collections of small molecules remains a major challenge to synthetic chemists. We illustrate the diversity-oriented synthesis (DOS) of small molecule collections to directly address this need, directed towards the search for new antibacterials with novel modes of action. Structurally-diverse and structurally-complex collections of compounds have been synthesised using solid-supported organic synthesis (using a novel diisopropyl silyl linker) and solution-phase organic synthesis (using purification handles). The chemistry involves catalytic asymmetric reactions. The chiral substrates are used as starting points from where more structural diversity can be generated, for example involving palladium–based cross couplings, ozonolysis, reductive amination, epoxidation, heterocycle formation, and ring-opening cross metathesis. The small molecule collections are screened against MRSA to look for novel targets for antibacterials.