Johnson Matthey recently integrated its biocatalyst offerings from X-Zyme, which Johnson Matthey acquired in July 2010. Johnson Matthey expanded the biocatalyst offerings into product and service offerings in its catalysis and chiral-technologies businesses. The portfolio from X-Zyme includes enzymatic catalysts for scalable production of highly pure chiral amines and alcohols. The biocatalysts and related technology complement the chemocatalytic technology and related expertise of Johnson Matthey. Also, in March 2010, the CDMO Cambrex acquired IEP, a technology company located in Wiesbaden, Germany, to build its portfolio for offering customized biocatalytic process development and sales of enzymes to the pharmaceutical industry.

Among pharmaceutical companies, Pfizer recently highlighted some improvements in API manufacturing routes, which included developing a biocatalytic route for pregabalin, the API in the pain treatment Lyrica (7, 9). A biocatalytic route and other green-chemistry improvements resulted in reducing solvent use by 5 million gallons per year and eliminating more than 150 tons of a nickel catalyst by using a third-generation synthesis in the manufacture of pregabalin. Other process improvements in other API manufacture involved a reduction by 65% of the total organic waste (3.5 million liters per year of methanol and tetrahydrofuran) and the elimination of liquid nitrogen in one step in manufacturing atorvastatin, the API in Pfizer's Lipitor. The company also eliminated 25,000 tons of waste per year in the manufacture of voricanazole, the API in Vfend through a green-chemistry modification in the manufacturing process. The synthesis used two innovative types of chemistry: an ultra-efficient synthesis of the key pyrimidinone intermediate and the development of a novel highly diastereoselective Reformatksy coupling reaction (9).

In general process improvements, Sigma-Aldrich recently reported on a route for manufacturing polyamino acids, which have properties that mimic proteins, thereby making them suitable for targeted drug delivery. Their production involves the intermediate amino acid N-carboxyanhydrides (NCAs) and polymer processing. For NCA production, the company eliminated repeated NCA recrystallizations and minimized manufacturing runs by 30%, and reduced the use of phosgene and tetrahydrofuran by 30% and ethyl acetate and hexane by 50% (7).

References

1. S.L. Zhang et al., Nat. Comm., DOI:10.1038/ncomms1214, Mar. 1, 2011.

2. S. Borman, Chem. & Eng. News 89 (10), 9 (2011).

3. J. Wang and B.L. Feringa, Science 331 (6023), 1429–1432 (2011).

4. B. Halford, Chem. & Eng. News 89 (7), 9 (2011).

5. E.J. Cho et al., Science 328 (5986), 1679–1681 (2010).

6. S. Buchwald et al., J. Am. Chem. Soc. 130 (41), pp 13552–13554 (2008).

7. EPA, The Presidential United States Environmental Protection Agency Green Chemistry Challenge Agency Awards Program Summary of 2010 Award Entries and Recipients (Washington DC, 2010).

8. Y. Tang et al., Chem. Biol. 16 (10), 1064–1074 (2009).

9. B. Kovats and K.Ball, Pharm. Technol. 33 (9), online exclusive (2009), http://pharmtech.findpharma.com/pharmtech/article/articleDetail.jsp?id=624208&pageID=1&sk=&date=, accessed Mar. 15, 2011.