Streamlining drug synthesis

Drug manufacture can benefit from flow synthesis, in which raw materials are fed into a sequence of reactors, producing the drug as a continuous output. A flow strategy that capitalizes on solid catalysts has now been realized. See Letter p.329 The continuous flow manufacturing systems that are the norm for the production of heavy chemicals are not generally used in the production of more complex and delicate fine chemicals and pharmaceuticals, where 'batch' processes remain the preferred method. This paper proposes a protocol that may bring the efficiency, safety and other benefits of continuous flow to the synthesis of drug-like molecules. Using only columns packed with heterogeneous catalysts, the authors passed commercially available starting materials successively through four columns containing achiral and chiral heterogeneous catalysts to synthesize the GABA-related anti-inflammatory drugs (R)-rolipram, (S)-rolipram and (R)-phenibut. The present multistep continuous flow synthesis runs at the laboratory scale, producing the drugs obtained on a gram scale; now work is under way to scale-up to multi-kilogram syntheses of drugs.