A Catalyst for Green Synthesis

A new book aims to inspire pharmaceutical chemists.
Dec 02, 2010

The central goal of Asymmetric Catalysis on Industrial Scale—Challenges, Approaches and Solutions, now in its second edition, is to show the organic chemist working in process research and development that enantioselective catalysis is not just an academic curiosity, but is suitable for large-scale production of enantioenriched intermediates. This book aims to be a source of information as well as an inspiration to chemists. The editors have gathered together 28 top-quality contributions which ably fulfill all of these goals.

Asymmetric Catalysis on Industrial Scale—Challenges, Approaches and Solutions, Hans-Ulrich Blaser and Hans-Jurgen Federsel, Eds., Wiley-VCH, Weinheim, Germany, 2010, 580 pp., ISBN: 978-3-52732-489-7
The book is organized into three major sections that reflect the various tasks facing the development or process chemist. The first five chapters make up a section titled "New Processes for Existing Active Compounds" that includes contributions from fine-chemical companies.

The chapters describe second-generation processes with an emphasis on developing the catalyst and the process. Authors also explain how to fit this process into production facilities. Of particular note is a contribution from scientists at Codexis, who describe the synthesis of a new class of cis-fused bicyclic proline derivatives through a relatively elegant enzyme-mediated asymmetric oxidative desymmetrization of prochiral amines.

The second section, "Processes for Important Building Blocks," encompasses 14 chapters that describe the development and production of the catalyst and catalytic process. The section includes contributions from fine-chemical companies, academia, and pharmaceutical manufacturers.

Many of the chapters within this section discuss state-of-the-art catalysts and how appropriate screening protocols can lead to initial findings that may be optimized as an efficient process. Noteworthy contributions include a topical assessment of various synthetic pathways to the rosuvastatin side-chain, and a discussion of the development of a novel continuous asymmetric hydrogenation process for the preparation of citronellal.

The book concludes with a group of chapters that examine "Processes for New Chemical Entities." These contributions from large pharmaceutical companies examine investigations of synthetic alternatives to key target molecules, route selection, and the integration of the catalytic step into the whole process. Companies such as Merck (Whitehouse Station, NJ), AstraZeneca (London), Abbott Laboratories (Abbott Park, IL), GlaxoSmithKline (London), and Hoffmann-La Roche (Basel) make valuable contributions to this section.

Chapters in each category provide a good mixture of examples that use various technologies. An obvious emphasis on asymmetric hydrogenation and biocatalysis reflects industry's comparatively greater adoption of these technologies. Examples of asymmetric phase-transfer catalysis, asymmetric catalytic nucleophilic ring opening, asymmetric conjugate addition to make carbon–carbon bonds, and Kagan oxidation to make chiral sulphoxides also are described. In the introduction, the editors provide a comprehensive analysis of these different technologies and catalysts, along with predictions for the future.

Some chapters focus on a single process, and others provide an overview of an applied technology. Many of the case studies effectively review the process of testing and rejecting various synthetic strategies, and explain how to optimize the chosen route to allow large-scale production. This strategy gives the reader valuable insight into the multiple aspects that must be considered when developing a process (e.g., technology efficiency, cost, development time, freedom to operate, equipment, and safety issues). Many of the chapters contain previously unpublished material or investigations that do not seem to have been reported in their entirety before.

This book excellently demonstrates that asymmetric catalysis is widely applied on an industrial scale and provides evidence that this application will continue to grow in coming years. The authors cite improved catalyst availability, efficiency, and increasing environmental pressure for catalytic processes as reasons that the technique will continue to find new users.

Overall, the second edition of this book is an excellent read for industrialists and academics alike. This volume certainly will not gather dust on anyone's bookshelf.

Karen E. Holt-Tiffin* is a head of biocatalysis, and Christopher J. Cobley is head of chemocatalysis, both at Chirotech Technology, Dr. Reddy's Custom Pharmaceutical Services,

*To whom all correspondence should be addressed.