Less waste in the synthesis of anti-inflammatory drugs

Dr Francesca Paradisi of the Centre for Synthesis and Chemical Biology (CSCB) at University College Dublin, and Professor Daria Giacomini and co-workers at the University of Bologna, Italy, have developed a highly efficient enzyme-driven process which could be applied to the synthesis of drugs such as Ibuprofen, avoiding the 50% waste of the undesired byproduct generated by current processes.

Their paper published in the Royal Society of Chemistry's Chemical Communications has been tagged as a hot article. Dr Paradisi and her co-workers used an enzyme called horse liver alcohol dehydrogenase to drive a process known as dynamic kinetic resolution (DKR). The researchers believe that this process could be applied to the synthesis of the Profen class of pharmaceutical products and that it represents a real move toward environmentally-friendly chemical processes.

The precursor to Ibuprofen, one of the most commonly used anti-inflammatory agents, is Ibuprofenol, which is a member of a class of molecules called arylpropanols. These molecules like many in nature occur in two forms; these are mirror images known as R and S, like right and left. But the biological activity of Ibuprofen is mainly due to the S form. Using conventional processes for preparing pure S-Ibuprofenol, a maximum conversion of only 50% is possible which is wasteful both economically and environmentally.

Kinetic resolution is based on the idea that the two forms of the molecules react at different rates. With DKR, it is possible to theoretically achieve 100% completion because both R and S forms of the starting material form a chemical equilibrium and exchange. In this way the faster reacting S form is replenished in the course of the reaction at the expense of the slower reacting R form, giving higher yields of the desired product.

Enzymes as biocatalysts offer many advantages over conventional chemical catalysts. The use of purified enzymes as reagents for organic synthesis is an important step in the development of environmentally benign or "greener" chemical processes.