Assessing the market
Researchers at the University of Bristol in England recently reported on an improved method for making prostaglandins, natural, hormone-like chemicals that have pharmaceutical applications. The prostaglandin analog latanoprost, which is used to treat glaucoma and ocular hypertension, is a well-known prostaglandin. It is the active ingredient in Pfizer's Xalatan, which generated 2011 sales of $1.25 billion; the patent for the drug expired in 2011 (1).
Due to prostaglandins' biological activity, but difficulty in synthesizing them, strategies for better synthetic routes for prostaglandins are an active area of research. For example, the current synthesis of latanoprost requires 20 steps and uses the methodology and strategy developed by E.J. Corey, winner of the 1990 Nobel Prize in Chemistry, according to an Aug. 15, 2012, University of Bristol press release.
The University of Bristol researchers reported on a synthesis of prostaglandin PGF2α, which relies on the use of an organocatalyst, a small organic molecule, to catalyze a key step in the process, which produced high levels of control of relative and absolute stereochemistry and fewer steps, according to the university press release and recent article detailing the research (2). The new process uses a new disconnection that enabled the researchers to complete the synthesis in only seven steps, according to the university release. The key step is an aldol cascade reaction of succinaldehyde using proline organocatalysis to create a bicyclic enal in one step with enantiomeric excess of 98%. This intermediate bicyclic enal is fully primed with the appropriate functionality for attachment of the remaining groups (1). The route to the bicyclic enal is important for a more efficient and potentially cost-effective route but also serves as a basis for examining related chemical structures of prostaglandin analogs (1, 2).
"Despite the long syntheses and the resulting huge effort that is required for the preparation of these molecules, they are still used in the clinic because of their important biological activity, said Varinder K. Aggarwal, professor in the School of Chemistry, University of Bristol, in the university release. "Being able to make complex pharmaceuticals in a shorter number of steps and, therefore, more effectively, would mean that many more people could be treated for the same cost."