Strategies in API Scale Up - Pharmaceutical Technology

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Strategies in API Scale Up
Process chemists employ a variety of approaches to improve yield, purity, and stereoselectivity.


Pharmaceutical Technology
Volume 37, Issue 1, pp. 52-54

Aromatic nitration reactions

Biocatalysis can play an important role in synthetic chemistry by providing more efficient chemical transformations and improving process conditions. Such is the case for chemists at the University of Warwick in the United Kingdom, who in collaboration with researchers at Cornell University in New York, recently reported on the discovery of an enzyme in the bacterium Streptomyces scabies that catalyzes an aromatic nitration reaction (6).


Drug development focus: orphan drugs
The researchers assert that TxtE, a cytochrome P450 enzyme, is the first example of an enzyme that has specifically evolved to catalyze an aromatic nitration reaction, according to a Sept. 21, 2012, University of Warwick, press release. It does this by using the gases nitrogen monoxide, generated from the amino acid arginine by the nitric oxide synthase partner enzyme txtD, and dioxygen. Engineering of the TxtE enzyme may allow it to be developed as a nitration biocatalyst for the production of industrial chemicals without the need to use nitric acid.

Cytochrome P450 enzymes are widespread in living organisms. Usually, they are responsible for hydroxylation and other oxidative reactions, but this is the first time that they have been reported to catalyze a nitration reaction, according to the researchers. TxtE catalyzes the introduction of a nitro group into a specific position of the aromatic ring of the amino acid tryptophan. This is the first key step in the biosynthesis of thaxtomin A.

Patricia Van Arnum is a executive editor of Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830
tel. 732.346.3072,
. twitter@PharmTechVArnum

References

1. "Catalyst: Putting Cyanide to Work", A*Star Research, online, http://www.research.a-star.edu.sg/research/6566/, Oct. 10, 2012.

2. A.M. Seayad et al., Chemistry–A European Journal 18 (18), 5693–5700 (2012).

3. I. Marek et al, Nature 490 (7421), 522–526 (2012).

4. B.E. and N. Cramer, Science 338 (6106), 504–506 (2012).

5. C. Zhu and S.P. Cook. J. Am. Chem. Soc. 134 (33), 13577–13579 (2012).

6. G. Challis, Nature Chem. Biol. 8 (10), 814–816 (2012).


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