Enzymatic synthesis of chiral intermediates for Omapatrilat, an antihypertensive drug

Biomolecular Engineering
R N Patel

Abstract

Biocatalytic processes were used to prepare chiral intermediates required for the synthesis of Omapatrilat 1 by three different routes. The synthesis and enzymatic conversion of 2-keto-6-hydroxyhexanoic acid 3 to L-6-hydroxynorleucine 2 was demonstrated by reductive amination using beef liver glutamate dehydrogenase. To avoid the lengthy chemical synthesis of the ketoacid 3, a second route was developed to prepare the ketoacid by treatment of racemic 6-hydroxy norleucine [readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin 4] with D-amino acid oxidase from porcine kidney or Trigonopsis variabilis followed by reductive amination to convert the mixture completely to L-6-hydroxynorleucine in 98% yield and 99% enantiomeric excess (e.e.). The enzymatic synthesis of (S)-2-amino-5-(1,3-dioxolan-2-yl)-pentanoic acid (allysine ethylene acetal, 5) was demonstrated using phenylalanine dehydrogenase (PDH) from T. intermedius. Phenylalanine dehydrogenase was cloned and overexpressed in Escherichia coli and Pichia pastoris. Using PDH from E. coli or P. pastoris, the enzymatic process was scale-up to prepare kg quantity of allysine ethylene acetal 5. The reaction yields of >94% and e.e. of >98% were obtained for allysine ethylen...Continue Reading

References

Mar 1, 1991·Journal of Cardiovascular Pharmacology·A A SeymourB Abboa-Offei
Jan 1, 1990·Critical Reviews in Biotechnology·H G DaviesS M Roberts
Jun 1, 1982·Archives of Biochemistry and Biophysics·C T HouN Barnabe
Apr 1, 1993·Enzyme and Microbial Technology·A L Margolin
Jan 19, 1999·Annual Review of Microbiology·R N Patel
Dec 1, 1999·Bioorganic & Medicinal Chemistry·R L HansonL J Szarka

❮ Previous
Next ❯

Citations

Aug 13, 2008·Applied Biochemistry and Biotechnology·Yangqiu LiuJichu Yang
Dec 17, 2002·Current Opinion in Biotechnology·Adrie J J StraathofAndreas Schmid
Feb 8, 2006·Applied and Environmental Microbiology·Seung-Goo LeeMoon-Hee Sung
Feb 17, 2009·Biochemistry. Biokhimii︠a︡·S V Khoronenkova, V I Tishkov
Aug 8, 2008·Microbial Cell Factories·Beate Pscheidt, Anton Glieder
Dec 12, 2013·Bioprocess and Biosystems Engineering·Jixian HouJichu Yang
Aug 2, 2003·Biotechnology Progress·Phillip R GibbsRichard C Willson
Feb 1, 2008·Expert Opinion on Drug Discovery·Ramesh N Patel
May 16, 2009·Biotechnology Advances·J D CarballeiraJ V Sinisterra
Feb 11, 2005·Biochemistry. Biokhimii︠a︡·V I Tishkov, S V Khoronenkova
Aug 22, 2016·Bioorganic Chemistry·Anju ChadhaSantosh Kumar Padhi
Feb 16, 2008·Nature Protocols·Andrew M KellyTony D James
Oct 19, 2016·Biotechnology and Applied Biochemistry·Alexandra LerchnerArne Skerra
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Sergio Martínez-RodríguezEsperanza Ortega
Jun 12, 2012·Physical Chemistry Chemical Physics : PCCP·Kornelia GawlitzaRegine von Klitzing
Jun 23, 2011·Chemical Reviews·Mélanie Hall, Andreas S Bommarius
Apr 5, 2013·Journal of the American Chemical Society·Michael RothmannMichael D Burkart

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.