← Back to Search
Biocatalysis For The Production Of Pharmaceutical Intermediates: Statin Precursors
Anera Švarc, Dino Skendrović, Ana Vrsalović Presečki
Published 2019 · Chemistry
Download PDFAnalyze on Scholarcy
The application of enzymes in chemical synthesis, due to the recent advances, has a strong impact in multiple industries, especially the pharmaceutical industry. Namely, the use of enzymes shows remarkable advantages over classical chemical catalysis and therefore it is considered a ‘green’ solution. By using novel techniques, it is possible to tailor the enzymes to adapt them for a given process. Today, several pharmaceutical companies are successfully producing valuable precursors for the production of active pharmaceutical ingredients using enzymes, some of them being statin precursors. Statins are hypolipidemics, drugs used for the prevention of cardiovascular diseases and lowering cholesterol concentration in blood. Due to challenges in the chemical synthesis of statin intermediates, the production of statin intermediates using enzyme-catalysed reactions shows some notable advantages. Therefore, research and development laboratories, combined with reaction engineering techniques, have shifted their focus towards applying biochemical catalysis for the production of statin intermediates.
This paper references
Process considerations for the scale-up and implementation of biocatalysis
Pär Tufvesson (2010)
Safety of statins
D. Maji (2013)
Truppo, Biocatalysis in the Pharmaceutical Industry: The Need for Speed, ACS Med
M D. (2017)
Design by Directed Evolution.
F. Arnold (1998)
Chemoenzymatic Methods for the Synthesis of Statins and Statin Intermediates
Kinetic modelling of aldolase-catalyzed addition between dihydroxyacetone phosphate and (S)-alaninal
Trinitat Suau (2008)
Process for the preparation of epoxide intermediates for pharmaceutical compounds such as statins
E. Mundorff (2007)
Engineered, highly productive biosynthesis of artificial, lactonized statin side-chain building blocks: The hidden potential of Escherichia coli unleashed.
Tadeja Vajdič (2014)
Optimization of a Crude Deoxyribose-5-phosphate Aldolase Lyzate-Catalyzed Process in Synthesis of Statin Intermediates
A. Ručigaj (2013)
Sequential Three- and Four-Substrate Aldol Reactions Catalyzed by Aldolases.
H. J. M. Gijsen (1995)
Chemoenzymatic Synthesis of Building Blocks for Statin Side Chains
M. Mueller (2005)
Sequential aldol condensation catalyzed by DERA mutant Ser238Asp and a formal total synthesis of atorvastatin
Junjie Liu (2004)
Chemoenzymatic synthesis of building blocks for statin side chains.
M. Müller (2005)
Synthesis of Sitagliptin, the Active Ingredient in Januvia® and Janumet®
Jaume Balsells (2010)
Statini u prevenciji i liječenju zloćudnih bolesti
Hrvoje Rimac (2015)
Historic Overview and Recent Advances in the Synthesis of Super-statins
Zdenko Časar (2010)
Rhodium(I)-catalyzed reductive carbon-carbon bond formation.
Adam D. J. Calow (2019)
Chemical and enzymatic approaches to the synthesis of optically pure ethyl (R)-4-cyano-3-hydroxybutanoate
Zhong-Yu You (2013)
Environmental biocatalysis: from remediation with enzymes to novel green processes.
M. Alcalde (2006)
D. Mink (2007)
Versatile and Efficient Immobilization of 2-Deoxyribose-5-phosphate Aldolase (DERA) on Multiwalled Carbon Nanotubes
Fabiana Subrizi (2014)
Saskia Bonjour (1824)
The Development of Short, Efficient, Economic, and Sustainable Chemoenzymatic Processes for Statin Side Chains
Martin Schuermann (2010)
Mevalonate pathway: a review of clinical and therapeutical implications.
I. Buhăescu (2007)
Enantioselective C-C bond synthesis catalysed by enzymes.
Joly Sukumaran (2005)
Sequential Aldol Condensation Catalyzed by Hyperthermophilic 2-Deoxy-d-Ribose-5-Phosphate Aldolase
H. Sakuraba (2007)
The Relationships between Cholesterol and Suicide: An Update, ISRN Psychiatry
D. De Berardis (2012)
E factors, green chemistry and catalysis: an odyssey.
R. Sheldon (2008)
Microbial aldolases as C–C bonding enzymes—unknown treasures and new developments
A. K. Samland (2006)
Enhancing the biocatalytic manufacture of the key intermediate of atorvastatin by focused directed evolution of halohydrin dehalogenase
Yu Luo (2017)
G.V.T.V. Weerasooriya (1824)
Biocatalytic synthesis of atorvastatin intermediates
J. Patel (2009)
Biocatalysis in development of green pharmaceutical processes.
J. Tao (2009)
Mayo , De Novo Design of Bio - catalysts
R. Blomberg (2002)
Biocatalysis, in W
Q. Wu (2012)
Seguin Hen (1824)
Statins as Potentially Neuroprotective Agents: A Review
Anuradha Patel (2012)
Mathematical model for aldol addition catalyzed by two D-fructose-6-phosphate aldolases variants overexpressed in E. coli.
M. Sudar (2013)
Improvement of aldehyde tolerance and sequential aldol condensation activity of deoxyriboaldolase via immobilization on interparticle pore type mesoporous silica
Takayuki Y. Nara (2011)
Introduction to the
J. D. Hostettler (1983)
Laboratory evolution of stereoselective enzymes: a prolific source of catalysts for asymmetric reactions.
M. Reetz (2011)
The Catalytic Asymmetric Aldol Reaction
T. Machajewski (2000)
Catalytic Promiscuity of Halohydrin Dehalogenase and its Application in Enantioselective Epoxide Ring Opening
Ghannia Hasnaoui‐Dijoux (2008)
Primary Prevention of Cardiovascular Disease with Statins in the Elderly
Ž. Reiner (2014)
Hagelüken , Markets for the Catalyst Metals Platinum , Palladium and Rhodium , Metall
R. Ballini (2006)
Structural Mechanism for Statin Inhibition of HMG-CoA Reductase
E. Istvan (2001)
The Relationships between Cholesterol and Suicide: An Update
D. De Berardis (2012)
2-Deoxyribose-5-phosphate aldolase from Thermotoga maritima in the synthesis of a statin side-chain precursor: characterization, modeling and optimization
A. Švarc (2019)
Markets for the catalyst metals platinum, palladium and rhodium
C. Hagelüken (2006)
Vrsalović-Presečki, Modeling as a Tool of Enzyme Reaction Engineering for Enzyme Reactor
Đ. Vasić-Rački (2011)
Adam S. Opalski (1824)
Biochemical engineering in biotechnology (Technical Report)
M. Moo-Young (1994)
Transition Metal Catalysis in the Pharmaceutical Industry
C. Busacca (2012)
The Development of Short, Efficient, Economic, and Sustainable Chemoenzymatic Processes for Statin Side Chains, in P
M. Schürmann (2010)
The Catalytic Asymmetric Aldol Reaction.
Recent advances on halohydrin dehalogenases—from enzyme identification to novel biocatalytic applications
A. Schallmey (2016)
Development of an efficient, scalable, aldolase-catalyzed process for enantioselective synthesis of statin intermediates.
W. A. Greenberg (2004)
Directed Evolution of Protein Catalysts.
Cathleen Zeymer (2018)
Pharmaceutical Intermediates by Biocatalysis: From Fundamental Science to Industrial Applications
Ramesh N. Patel (2016)
A historical perspective on the discovery of statins
A. Endo (2010)
A Highly Productive, Whole-Cell DERA Chemoenzymatic Process for Production of Key Lactonized Side-Chain Intermediates in Statin Synthesis
Matej Ošlaj (2013)
Recent advances in biocatalyst development in the pharmaceutical industry
M. M. Zhang (2013)
Modelling as a tool of enzyme reaction engineering for enzyme reactor development
D. Vasić-Rački (2011)
Efficient synthesis of a statin precursor in high space-time yield by a new aldehyde-tolerant aldolase identified from Lactobacillus brevis
Xue-Cheng Jiao (2015)
Improving enzymes by using them in organic solvents
Alexander M. Klibanov (2001)
Principles, techniques, and applications of biocatalyst immobilization for industrial application
Ismail Eş (2015)
Directed evolution of industrial enzymes: an update.
J. R. Cherry (2003)
Industrial Applications of Enzymes: Recent Advances, Techniques, and Outlooks
Jordan M Chapman (2018)
De novo enzymes by computational design.
Hajo Kries (2013)
Gruber-Khadjawi, Biocatalytic Methods for C−C Bond Formation
M. K. Fesko (2013)
Enzyme-mediated oxidations for the chemist
F. Hollmann (2011)
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion
A. Fürstner (2016)
Advances in biocatalytic synthesis of pharmaceutical intermediates.
S. Panke (2005)
A green-by-design system for efficient bio-oxidation of an unnatural hexapyranose into chiral lactone for building statin side-chains
Xue-Cheng Jiao (2016)
Protection for the Thiol Group, in P
P. Wuts (2006)
Axel M. Gressner (2012)
Drug interactions with statins
A. Čaušević-Ramoševac (2013)
Biocatalysis for pharmaceutical intermediates: the future is now.
D. Pollard (2007)
Characterization and application of a newly synthesized 2-deoxyribose-5-phosphate aldolase
Zhong-Yu You (2012)
Protection (and deprotection) of functional groups in organic synthesis by heterogeneous catalysis.
G. Sartori (2004)
The discovery of biological enantioselectivity: Louis Pasteur and the fermentation of tartaric acid, 1857--a review and analysis 150 yr later.
J. Gal (2008)
Biocatalytic Methods for C—C Bond Formation
Kateryna Fesko (2013)
Lessons from 60 years of pharmaceutical innovation
B. Munos (2009)
Enzyme Immobilization: The Quest for Optimum Performance
R. Sheldon (2007)
Integrating enzyme immobilization and protein engineering: An alternative path for the development of novel and improved industrial biocatalysts.
C. Bernal (2018)
Biochemical and biocatalytic characterization of 17 novel halohydrin dehalogenases
J. Koopmeiners (2016)
An industrially applied biocatalyst: 2-Deoxy-d-ribose-5- phosphate aldolase
Hui Fei (2017)
Effect of the Principal Nutrients on Simvastatin Production by Wild Strain Aspergillus terreus 20 in Submerged Fermentation
S. M. Nasmetova (2015)
Kinetic modeling of a crude DERA lysate-catalyzed process in synthesis of statin intermediates
Aleš Ručigaj (2015)
Enantioselective formation and ring-opening of epoxides catalysed by halohydrin dehalogenases.
D. Janssen (2006)
Engineering the third wave of biocatalysis
U. Bornscheuer (2012)
Directed evolution of an industrial biocatalyst: 2-deoxy-D-ribose 5-phosphate aldolase.
S. Jennewein (2006)
A process for the preparation of 2- (6-substituted 1,3-dioxane-4-yl) acetic acid derivatives
D. Mink (2001)