Let enzymes do the work

The use of enzymes is having a major impact on the synthesis of pharmaceutical ingredients in terms of yield. Dr Sarah Houlton highlights some recent successes.

The ability to harness the power of nature in the form of enzymes has had a real impact on the synthesis of pharmaceutical ingredients in recent years. These white biotechnology applications have made it possible to improve some syntheses – often dramatically – and even make some molecules that would otherwise be either impossible or impractical to synthesise.

Many standard chemical reactions can now be achieved using enzyme catalysts. One recent example from the labs of CLEA Technologies in Delft, Netherlands, is the use of Pseudomonas stutzeri lipase, or PSL, to carry out aminolysis reactions.¹ It proved particularly effective on sterically hindered substrates. The current common techniques for carrying out aminolysis reactions predominantly use acid chlorides or coupling reagents. These tend to be non-catalytic and not very atom efficient, with toxic or corrosive reagents or by-products. Using an enzyme catalyst would improve the process’s green credentials.

The researchers took a range of bulky methyl esters and amines as substrates – the acyl donors were activated as methyl esters to avoid salts forming between the amine and the carboxylic acid. For comparison, the same substrates were also treated with Novozym 435, an immobilised Candida Antarctica lipase B. While the CAL-B enzyme was more efficient in those aminolysis reactions where methyl 2-phenylpropionate was the acyl donor, for secondary amines PSL worked better, as it did with piperidine.