Chiral Chemistry

This week's cover story on chiral chemistry—which consists, in fact, of three related stories—is a feast of chemistry. Senior Correspondent Ann Thayer examines three aspects of developing applications of chiral molecules: chiral catalysis in the synthesis of active pharmaceutical ingredients (APIs), the use of supercritical fluid chromatography (SFC) for separating enantiomers, and methods for removing traces of metals from pharmaceutical products. It is hard to imagine packing more practical chemistry into 12 pages of any magazine, even C&EN.

"Catalytic approaches to producing chiral molecules—be they organometallic, organocatalytic, or biocatalytic—highlight the ingenuity of chemists in designing not only reactions, but the reactants as well," Thayer writes. "Along with new technologies, such as SFC, chemists continue to delve deeper into an immense pool of chemical diversity to create new drug compounds."

The first article, on chiral catalysis, is the heart of the package of chemistry that Thayer provides. "Catalysis for asymmetric reactions is generating tremendous academic and industrial interest, even if it is not yet widely used in pharmaceutical production," Thayer notes. Until relatively recently, many chiral drugs were simply delivered as racemates. Under regulatory and commercial pressure, some chiral drugs have been developed as pure enantiomers using a number of approaches to obtain the desired stereoisomer.

Thayer surveys a broad range of chemical reactions, catalysts, and experimental techniques in the article. One company she cites is Merck, which, she writes, "established a simple goal when creating its catalysis lab a few years ago—namely, the early and rapid implementation of efficient catalytic processes in API synthesis." Initially emphasizing asymmetric hydrogenation, the company "replaced ad hoc efforts with a centralized catalysis lab that works closely with the project chemists who design overall synthetic routes."

Thayer also looks at work being done at Pfizer. The name of a C1-symmetrical bisphosphine ligand designed by the Pfizer group—trichickenfootphos—caught my eye. For simplicity, the versatile ligand goes by the acronym TCFP, but that wonderfully descriptive name captures a little of the whimsy that, in part, motivates chemists.

Much remains to be learned about chiral catalysis. Thayer quotes Thomas Riermeier of Degussa Homogeneous Catalysts as saying, "I think we are far from having a general understanding of asymmetric homogeneous hydrogenation after 30 years of research."

In the second story, Thayer examines the use of SFC for the preparative-scale separations of enantiomers. Chromatographic separations are the exception rather than the rule in producing chiral pharmaceuticals, Thayer notes, but regulatory concerns have necessitated the isolation and testing of the enantiomers of potential chiral drugs. SFC offers many advantages over traditional chromatographic approaches.

"Nothing comes without a hidden cost or flip side," Thayer quotes Christopher J. Welch, head of the analysis and preparative separations group at Merck in the third of the cover stories. "Asymmetric catalysis is a great boon but carries with it the problem of having to deal with residual metals." Of course, chemists are there to supply ingenious solutions to this challenge, too.

As informative and valuable as Thayer's article is in the print edition of C&EN, the C&EN Online version is even more valuable. How so? The C&EN Online version provides links to all of the cited papers from ACS journals, Royal Society of Chemistry journals, and Angewandte Chemie. Those links take you directly to the full text of the journal article, for free. I count nearly 30 such references. That's quite a deal.

The lead news story in this week's issue concerns the devastation wrought by Hurricane Katrina (see page 11). All of our hearts go out to the millions of people who have been affected by Katrina. James D. Burke, chair of the ACS Board of Directors, urges ACS members to give generously to relief organizations assisting the victims of the storm. He also says that, in the coming months, ACS will conduct needs assessments of local sections in the affected areas and will be working with them in their recovery efforts.

Thanks for reading.