Catalyzing the Synthesis - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Catalyzing the Synthesis
Researchers develop various catalytic approaches for improving yield, purity, stereoselectivity, and process conditions.


Pharmaceutical Technology
pp. 44-50


IMage: Jason Reed / GETTY
Catalysts play an important role in chemical reactions, but they are particularly important in producing fine chemicals or pharmaceutical compounds to meet desired yields, purity, and stereoselectivity. Elucidating how a catalyst may work in a specific synthesis is not only valuable for a given project, but it contributes to an overall understanding of process chemistry. Some recent advances involve asymmetric synthesis and approaches for improved enantioselectivity, oxidation catalysis, and the development of boron-based ligands.

Improving enantioselectivity


Patricia Van Arnum
Researchers at the University of Amsterdam recently reported on an approach for identifying and developing catalysts to synthesize products with high enantioselectivity, a method of utility for making pharmaceutical compounds. The researchers reported on the development of an achiral bisphosphine rhodium complex, which contained a binding site for recognizing chiral anion "guests" or cofactors. Upon binding the small-molecule cofactors, the rhodium complex becomes chiral and can then be used in asymmetric catalysis. The researchers screened a library of cofactors and discovered the optimal cofactors, which led to the identification and development of hydrogenation catalysts that formed products with enantiomeric excess as high as 99%. The researchers also conducted a competition experiment to determine the optimal cofactor among a mixture of 12 cofactors. The optimal cofactor was one that binds strongest to the rhodium complex (i.e., the catalyst) and through the catalyst produced the product with greatest optical purity. The competition experiment provided the basis for creating an efficient way to screen a library of cofactors with other metal–ligand systems (1, 2). The University of Amsterdam chemists have patented the strategy and plan to develop it alongside their other high-throughput ligand-screening strategies through a spin-off company, InCatT.

Raising the bar in catalytic hydrogenation


Formulation development forum: translational pharmaceutics (FIGURE 1 IS COURTESY OF THE AUTHOR)
Researchers at the University of Alberta recently developed a new ruthenium-aminophosphine catalyst with very high turnover. The catalyst system was used for the hydrogenation of a variety of acyclic and cyclic amides to the corresponding alcohols and amines. They reported catalytic activity with turnover as high as 7200. Specifically, the researchers reported that the reaction between 2 equivalents of Ph2P(CH2)2NH2 and cis-[Ru(CH3CN)2 (η3-C3H5) (cod)]BF4 (cod = 1,5-cyclooctadiene) formed a highly active catalyst precursor for the selective hydrogenation of amides. The reaction proceeded with good atom economy, yield, and turnover under moderate reaction conditions (3). The researchers are working to further optimize the catalyst system, according to a Sept. 28, 2011, University of Alberta press release.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
28%
Oversee medical treatment of patients in the US.
12%
Provide treatment for patients globally.
9%
All of the above.
45%
No government involvement in patient treatment or drug development.
7%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
Source: Pharmaceutical Technology,
Click here