Indole synthesis route ‘will cut costs’

A new reaction to form the carbon skeleton of an indole molecule could reduce costs and help cut toxic by-products in pharmaceutical synthesis, as well as speeding up drug development, claim its developers at the University of Toronto.

Previous indole syntheses have required six to ten steps, says the reaction’s designer, Mark Lautens; the new scheme needs only three.

Indoles are ring structures containing carbon and nitrogen, and are common groups in pharmaceutical active ingredients, particularly in cholesterol-lowering drugs.

Lautens’ synthesis, developed with graduate student Eric Fang, uses a metallic element as a catalyst to form two chemical bonds, leading to a wide range of indole-containing compounds. The university has filed a provisional patent for the process.

The savings produced from using the simplified synthesis could be dramatic, Lautens says.

‘In order to make a hundred kilogrammes of these best-selling drugs, there are often hundreds of litres of solvent used, not to mention the many purification processes involved,’ he says. ‘Not only are you speeding up the process, you’re also reducing waste and energy used in manufacturing.’