Loading ePaper
Enzyme-based Catalysis A Straightfoward Way to New Chiral Building Blocks 03
Gute Chemie. Connects. Your abcr Team.
Gute Chemie. Foreword 3 Gute Chemie. Welcome to abcr. What do you think of when you hear the expression ‚Gute Chemie‘? Does it make you think of top-quality products or people that understand each other really well? Since we set up our company in 1987, we have consistently attempted to combine both. We offer Gute Chemie in the form of more than 400,000 specialty chemicals that we supply to major pharmaceuticals and chemical companies. And we also provide Gute Chemie in terms of our personal service coupled with an extensive network that links our clients, suppliers and partners all around the world. With this brochure, we would like to invite you to experience all the aspects of Gute Chemie. Dr. Jan Schuricht | Managing Director
The company. Gute Chemie comes from abcr. abcr GmbH Germany abcr Locations Worldwide
Gute Chemie. abcr 2 | 5 With abcr, you have access to over 400,000 products from the organic, organometallic and inorganic specialty chemical areas. You can order all of these materials conveniently via our webshop and we keep a large portion of them on stock for you in our logistics centre. Should your desired product not be among them, we will seek out a suitable manufacturer in our international network, or synthesise it in our own laboratories. Working with all sectors Specialisation as standard: our key business fields Pharmaceutical and chemical companies, research labs and universities: our range of products is as diverse as the customers that use them. Applications for abcr’s specialty chemicals include synthesis and catalysis in the life sciences, medicinal chemistry and surface technology areas. We are constantly updating and expanding our product range in line with the progress in research and development. › R&D services: custom synthesis, research projects and abcr product line from our laboratory - Made in Germany › Production: research, process development, scale-up in multi tons scale, syntheses and contract manufacturing from our production facilities - Made in Europe › Bulk business: procurement, scale up and sales of raw materials for your production › Catalogue business: procurement and sales of specialty chemicals, more than 400.000 products easily found in our webshop › Small quantity supply: sample and small quantity sales for products of well-known partners › Services: central warehouse and logistics certified for storage of hazardous materials, daily filling and decanting from grams to tons In our catalogue business you will find following product portfolio: Silanes & Silicones Fluoro Compounds Organometallics Ionic Liquids Monomers & Polymers Biochemistry Reagents Boronic Acids & Esters Specialty Gases Amino Acids Phosphines Catalysts & Ligands Nanomaterials Ceramic Powders Precious Metal Compounds High Purity Metals Rare Earth Compounds Building Blocks Deuterated Compounds Sol-gel Precursor CVD Precursor Solvents
Gute Chemie. The Biocatalytic Toolbox from Enzymicals Enzyme-based catalysis – a straightfoward way to new chiral building blocks In the past, many of the classical catalyzed processes were based on noble metal catalysis. Enviro- mental friendly catalytic systems seek to replace noble metals by organocatalysts or earth-abundant transition metals. Enzymatically catalzyed processes are still quite rare in chemical industry, but offer an interesting extension of the catalyst toolboxes and a straightforward way to a wide variety of valuable chiral compounds. Together with our partner Enzymicals, abcr can offer a broad enzyme selection. The enzyme portfolio of Enzymicals provides a continually expanding toolbox with innovative biocatalysts and a range of proteins is offered. All catalog enzymes are available from stock and are offered as recombinant produced crude protein extracts from microbial host systems in technical grade. Final formulations, as well as higher grades of purity, can be adapted on request to meet specific process requirements. All enzymes are available in bulk scale. © Enzymicals AG© Enzymicals AG
Gute Chemie. The Biocatalytic Toolbox from Enzymicals 4 | 7 © Enzymicals AG© Enzymicals AG
Gute Chemie. Products 9 Product Line Enzyme-based Catalysis. Table of contents. Esterases Recombinant Pig Liver Esterases Recombinant Esterases Lipases Baeyer-Villiger Monooxygenases (BVMOs) Amine Transaminases Imine Reductases (IREDs) Halohydrin Dehalogenases (HHDHs) Phosphotransferases Selected Chiral Compounds 11 23 27 33 37 41 45 47
Gute Chemie. Esterases 11 Gute Chemie. Esterases Esterases represent a diverse group of hydrolases catalyzing the cleavage and formation of ester bonds. Carboxylesterases (EC 3.1.1.1) are a subset of esterases that specifically hydrolyse carboxylic esters to give two products: a carboxylic acid and an alcohol. Comment: For quality assurance recombinant pig liver and recombinant esterases are tested against p-nitrophenyl acetate as standard substrate at 30°C and pH 7.5. O O R3 R1 R2 Esterase OH H2O R1 R2 O + R3-COOH + O R3 R1 R2 Many of them show a wide substrate tolerance and also high regio- and stereospecificity, which make them attractive biocatalysts for the production of optically pure compounds for fine chemical synthesis. The interest in these enzymes also resides in the fact that they do not require cofactors, are stable and are even active in organic solvents. Preferred substrates are esters and short-chain triglycerides. References & Futher Information Hydrolases in Organic Synthesis. U.T. Bornscheuer and R.J. Kazlauskas, 2nd edition, Wiley-VCH (2005) abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
12 Gute Chemie
Gute Chemie. Recombinant Pig Liver Esterases 13 Gute Chemie. Recombinant Pig Liver Esterases The pig liver esterase (PLE) is a widely used enzyme in organic synthesis. Due to its ability to work under mild conditions and with organic solvents it is a very useful biocatalyst for the synthesis of optically pure compounds. Six of the identified isoenzymes of the pig liver esterase are now commercially available. The traditional use of isolates from pig liver had the disadvantage of being an ill-defined mixture of hydrolases including PLEisoenzymes. The application of single isoenzymes guarantees a reproducible enzyme activity and prevents undesired side reactions. The „Enzymicals recombinant expression platform“ ensures their animal free manufacturing and direct production scale-up. Final formulation can be adapted to meet specific process requirements. AB503565 Pig Liver Esterase isoenzyme 1, recombinant from E. Coli ■ Solid / lyophilized powder AB503566 Pig Liver Esterase isoenzyme 2, recombinant from E.Coli ■ Solid / lyophilized powder AB503567 Pig Liver Esterase isoenzyme 3, recombinant from E.Coli ■ Solid / lyophilized powder AB503568 Pig Liver Esterase isoenzyme 4, recombinant from E.Coli ■ Solid / lyophilized powder AB503569 Pig Liver Esterase isoenzyme 5, recombinant from E.Coli ■ Solid / lyophilized powder AB503570 Pig Liver Esterase isoenzyme 6, recombinant from E.Coli ■ Solid / lyophilized powder 9016-18-6 9016-18-6 9016-18-6 9016-18-6 9016-18-6 9016-18-6 AB503571 Pig Liver Esterases screening kit, recombinant from E.Coli, contains all six pig liver esterase isoenzymes (AB503565 - AB503570; 6 x 50mg) ■ Solid / lyophilized powder ■ For quick and easy identification of the best isoenzyme with respect to enantioselectivity and enantiopreference. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
14 An example for enantioselective resolutions and desymmetrizations with Pig Liver Esterase: R2 Pig Liver Esterase R2 R2 R1 COOR3 R1 COOH + R1 COOR3 O S R1 Pig Liver Esterase COOR2 O S R1 COOH + O S R1 COOR2 Examples for chiral products can be obtained from PLE-mediated hydrolysis of carboxylic esters in the abcr portfolio: AB206009 (1S,2R)-cis-4-Cyclohexene-1,2-dicarboxylic acid 1-monomethyl ester; 98% 88335-93-7 O O O AB506070 (1R,2S)-2-Methylcyclopentanecarboxylic acid 134877-06-8 AB506071 (1S,2R)-2-Methylcyclobutanecarboxylic acid 134877-05-7 OH O OH O OH Gute Chemie
Gute Chemie. Recombinant Pig Liver Esterases 15 All isoenzymes show high enantioselectivities and even opposite enantiopreferences in the kinetic resolution of several secondary alcohols (see figure). They also exhibit different specific activities towards chiral esters and offer diverse selectivities for the desymmetrization of prochiral compounds. 100 (S)-Enantiomer OAc OAc y t i v i t c e l e s o i t n a n E 80 60 40 20 20 40 60 80 OAc OAc 100 (R)-Enantiomer AB503565 AB503566 AB503567 AB503568 AB503569 AB503570 Fluka-PLE Enantioselectivity of PLE isoenzymes towards selected secondary alcohol esters. Data for Fluka-PLE refers to a commercially available enzyme preparation which contains a mixture of isoenzymes. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
16 Gute Chemie
Gute Chemie. Recombinant Esterases 17 Gute Chemie. Recombinant Esterases AB503572 – CAS 9016-18-6 Bacillus subtilis Esterase, recombinant from E.Coli Properties: ■ Removes tert-butyl ester protecting group, e.g. from peptides ■ Acts on tertiary alcohols in the kinetic resolution of racemic esters ■ Exhibits promiscuous amidase activity ■ Optimum conditions: 40°C, pH 8-9 ■ Solid / lyophilized powder An example of deprotection by AB503572 with various alcohol moieties: CbzN Cbz: OR O R: AB503572 CbzN O + ROH OH Chiral products can be obtained from hydrolysis of tertiary alcohol esters by variants of AB503572 in the abcr portfolio: AB506073 (2S)-1,1,1-Trifluoro-2-phenylbut-3-yn-2-ol 88445-11-8 AB506075 (2S)-1,1,1-Trifluoro-2-phenylbut-3-en-2-ol 152141-78-1 OH F OH F F F F F abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com OOClCCl3
18 AB503573 – CAS 9016-18-6 Bacillus subtilis Esterase, bacterial, recombinant from E.Coli Properties: ■ Acts on esters with medium chain length fatty acids ■ Good acceptance of branched alcohol moieties ■ Active towards several lactones ■ Optimum conditions: 40°C, pH 7.5-8 ■ Solid / lyophilized powder Examples of substrates hydrolyzed by AB503573: O O O O O O O O AB503574 – CAS 9016-18-6 Bacillus stearothermophilus Esterase, bacterial, recombinant from E.Coli Properties: ■ Active towards various carboxylic acid esters ■ Accepts substrates with sterically demanding carboxylic acid groups ■ Active towards several lactones ■ High temperature stability ■ Optimum conditions: 65°C, pH 7 ■ Solid / lyophilized powder Examples of substrates hydrolyzed by AB503574: O O O O O O O O AB503575 – CAS 9016-18-6 Pseudomonas fluorescens Esterase, bacterial, recombinant from E.Coli Properties: ■ Acts on a wide range of aliphatic and aromatic esters ■ Active and stable at elevated temperatures and in organic solvents ■ Can be used for acetylation reactions ■ Optimum conditions: 45°C, pH 7.5-8 ■ Solid / lyophilized powder Examples of substrates hydrolyzed by AB503575: O O HO O O HO O O O O O O Gute Chemie
Gute Chemie. Recombinant Esterases 19 AB503576 – CAS 9016-18-6 Pseudomonas fluorescens Esterase, bacterial, recombinant from E.Coli Properties: ■ Active towards various carboxylic acid esters and lactones ■ Optimum conditions: 43°C, pH 7.5 ■ Solid / lyophilized powder Examples of substrates hydrolyzed by AB503576: O O O O O O O O AB503577 – CAS 9016-18-6 Paenibacillus barcinonensis Esterase, recombinant from E.Coli Properties: ■ Active towards various carboxylic acid esters ■ Variants act on tertiary alcohols esters ■ Optimum conditions: 37°C, pH 7.5 ■ Solid / lyophilized powder Example of a stereoselective hydrolysis of tertiary alcohol esters by AB503577 variant: O O AB503577 O R4 R1 R3 R2 O R4 R1 R3 + R1 R2 OH R2 R3 + R4COOH AB503578 – CAS 9016-18-6 Pyrobaculum calidifontis Esterase, bacterial, recombinant from E.Coli Properties: ■ Active towards esters with short to medium chain length ■ Accepts straight and branched chain alcohols ■ Excellent enantioselectivity in the resolution of tertiary alcohol esters ■ Active in organic media ■ Optimum conditions: 90°C, pH 7 ■ Solid / lyophilized powder Examples of substrates hydrolyzed by AB503578: O O O O O O O O abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
20 AB503579 – CAS 9016-18-6 Nocardia farcinica Esterase, recombinant from E.Coli Properties: ■ Acts on a range of tertiary alcohols in the kinetic resolution of racemic esters ■ Excellent enantioselectivity (E>100) in the hydrolysis of menthyl acetate ■ Optimum conditions: pH 7.5 ■ Solid / lyophilized powder Example of a stereoselective hydrolysis of tertiary alcohol esters by AB503579: O O AB503579 O R4 R1 R3 R2 O R4 R1 R3 + R1 R2 OH R2 R3 + R4COOH AB503580 – CAS 9016-18-6 Methylobacterium populi Esterase, bacterial, recombinant from E.Coli Properties: ■ Acts on a range of tertiary alcohols in the kinetic resolution of racemic esters ■ Optimum conditions: pH 8.0 ■ Solid / lyophilized powder Example of stereoselective hydrolysis of tertiary alcohol esters by AB503580: O O AB503580 O R4 R1 R3 R2 O R4 R1 R3 + R1 R2 OH R2 R3 + R4COOH Gute Chemie
Gute Chemie. Recombinant Esterases 21 AB503581 – CAS 9016-18-6 Pelobacter propionicus Esterase, bacterial, recombinant from E.Coli Properties: ■ Acts on tertiary alcohols in the kinetic resolution of racemic esters ■ Optimum conditions: pH 7.5 ■ Solid / lyophilized powder Example of a stereoselective hydrolysis of tertiary alcohol esters by AB503581: O O AB503581 O R4 R1 R3 R2 O R4 R1 R3 + R1 R2 OH R2 R3 + R4COOH Esterase Kits AB503582 Esterase screening kit, bacterial, recombinant from E.Coli, contains all ten bacterial esterases (AB503572 - AB503581; 10 x 50mg) ■ solid / lyophilized powder AB503583 Esterase kit for tertiary alcohols, recombinant from E.Coli, contains eleven suitable esterases (AB503565 - AB503570, AB503572, AB503577, AB503579 - AB503581; 11 x 50mg) ■ solid / lyophilized powder AB503572 and AB503577: Several mutants with enhanced substrate specificity and/or increased stereoselectivity are available upon request. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
22 Gute Chemie
Gute Chemie. Lipases 23 Gute Chemie. Lipases Lipases (EC 3.1.1.3) catalyze the hydrolysis of water insoluble esters such as triglycerides like triolein to diolein. In addition, lipases also catalyze the hydrolysis of a broad range of natural and unnatural esters, while retaining high enantio- or regioselectivity. They require no cofactors and are simple to use. They act in water, biphasic and pure organic solvent systems as well as on water-insoluble substrates. AB503585 Candia antarctica lipase, microbial, recombinant from Pichia pastoris ■ Origins: Candia antarctica ■ Liquid / concentrated culture supernatant 9001-62-1 AB503587 Fusarium solani pisi lipase, microbial, recombinant from Bacillus subtilis ■ Origins: Fusarium solani pisi ■ Liquid / concentrated culture supernatant 9001-62-1 AB503588 Geobacillus thermoleovorans IHI-91 lipase, bacterial, recombinant from Corynebacterium glutamicum ■ Origins: Geobacillus thermoleovorans IHI-91 ■ Liquid / concentrated culture supernatant 9001-62-1 AB503589 Kurtzmanomyces spec. Lipase, microbial, recombinant from E.coli ■ Origins: Kurtzmanomyces spec. ■ Solid / lyophilized powder AB503591 Lipase screening kit, recombinant from different origins, contains all four lipases as liquid formulations (4 x 0.5ml) ■ Liquid / concentrated culture supernantant Bulk amounts available. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
24 Separation of trans and cis fatty acids by using a special engineered CAL-A variant: R1 n COOR2 R1 + COOR2 m n m R1 n C 2 m Protein engineering of lipase CAL-A led to the discovery of mutants with excellent chemoselectivity for the removal of trans and saturated fatty acids from partially hydrogenated vegetable oil. Diverse variants of CAL-A are available on request. References & Futher Information [Brundiek, H.B., Evitt, A.S., Kourist, R., Bornscheuer, U.T. (2012), Creation of a lipase highly selective for trans fatty acid by protein engineering, Angew. Chem. Int. Ed., 51, 412-414; Erzeugung einer für trans-Fettsäuren hochselektiven Lipase durch Protein-Engineering, Angew. Chem., 124, 425-428.] Gute Chemie
Gute Chemie. Lipases 25 This combination of broad substrate range and high selectivity makes lipases an ideal catalyst for organic synthesis. Chemists use lipase-catalyzed biotransformations for regio- and stereoselective transformation, to prepare enantiomerically-pure pharmaceuticals and synthetic intermediates, to protect and deprotect synthetic intermediates as well as for more specialized uses. Examples for very well described lipase catalyzed reactions in which the natural nucleophile – water – is replaced by an alcohol, hydroperoxide or amine are: ■ hydrolysis ■ esterification ■ aminolysis The lipase-catalyzed esterification reactions are among the most significant chemical and biochemical processes of industrial relevance due to an increased use of organic esters in biotechnology and the chemical industry. Example reactions catalyzed by lipase: a) Hydrolysis or esterification O Lipase O + R3OH R1 OR2 + R2OH R1 OR3 R1 = alkyl, etc. R2, R3 = H, alkyl, etc. ; R2 ≠ R3 b) Transesterification O R1 O Lipase O O + R3 O 4 O R3 + R1 O 4 O R1, R3 = alkyl, etc. ; R1 ≠ R3 R2, R4 = H, alkyl, etc. ; R2 ≠ R4 c) Aminolysis R1 RNH Lipase R1 NHR R References & Futher Information Hydrolases in Organic Synthesis. U.T. Bornscheuer and R.J. Kazlauskas, Wiley online libary, 2nd edition (2006) abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
26 Gute Chemie
Gute Chemie. Baeyer-Villiger Monooxygenases (BVMOs) 27 Gute Chemie. Baeyer-Villiger Monooxygenases (BVMOs) BVMOs are flavoenzymes and belong to the class of oxidoreductases. They catalyze the oxidation of linear, cyclic and aromatic ketones to esters or lactones, respectively, highly similar to the chemical Baeyer-Villiger oxidation. During the enzymatic oxidation, one atom of molecular oxygen is incorporated into a carbon-carbon bond of a non-activated ketone, whereas the other oxygen atom ends up in a water molecule with the hydrogen atoms originating from the cofactor NAD(P)H. O R1 R2 BVMO O2 H2O NAD(P)H NAD(P)* O O R1 R2 + R1 O R2 BVMOs are typically soluble proteins and work without additional proteins. Furthermore these enzymes require NADH or NADPH as cofactors. References & Futher Information References: Monooxygenases, Baeyer-Villiger oxidations in organic synthesis. J. Rehdorf and U. T. Bornscheuerin Encyclopedia of Industrial Biotechnology. Flickinger, Michael C. (ed.). Wiley-VCH (2010) Patent IN 2011CH01274 (Mylan Labs): Novel process for the preparation of rivastigmine via enzymic resolution of C1-4 carboxylic acid 1-(3-methoxy-phenyl)ethyl ester to (S)-ester using lipase enzyme abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
28 AB503593 – CAS 52037-90-8 Acinetobacter calcoaceticus Monooygenase, bacterial, recombinant from E. Coli Properties: ■ Baeyer-Villiger-Oxidation of aliphatic and alicyclic ketones ■ High regio- and enantioselectivity ■ NADPH-dependent ■ Liquid / formulation with glycerin Comment: For quality assurance AB503593 is tested against benzylacetone as standard substrate at 30°C and pH 8.5. Examples of chiral products obtained from reactions catalyzed by AB503593 with isolated enzyme or whole cell systems: O O R R O O O O R R R = Cyclopropyl / 57%; ee >99% (+) R = cis-OH / 88%; ee >98% (-) R = trans-OH / 80%, ee >96%(+) R = 4-Cl-Ph / 88%; ee 85% (+) R = 3-MeO-Bn / 83%; ee 96% (-) R = 3,4-(OCH2O)-Bn / 83%; ee 95% (-) R = Me, Et / >70%; ee >93% (+) R = CH2OCH2 / 74%; ee >98% (+) AB503594 – CAS 1005768-90-0 Thermobifida fusca Monooxygenase, bacterial, recombinant from E. Coli Properties: ■ Baeyer-Villiger-Oxidation of aromatic and aliphatic ketones ■ Able to perform sulfur oxidations ■ Moderate thermostability ■ High regio- and enantioselectivity ■ NADPH-dependent ■ Liquid / formulation with glycerin Comment: For quality assurance AB503594 is tested against benzylacetone as standard substrate at 30°C and pH 8.5. Examples of chiral products obtained from reactions catalyzed by AB503594 with isolated enzyme or whole cell systems: O O MeO O O O HN OMe O O ee 97% ee 95% ee > 99% Gute Chemie
Gute Chemie. Baeyer-Villiger Monooxygenases (BVMOs) 29 AB503595 – CAS 1005768-90-0 Thermobifida fusca Monooxygenase, bacterial, recombinant from E. Coli Properties: ■ Baeyer-Villiger-Oxidation of aromatic ketones and amines ■ Able to perform sulfur oxidations ■ Moderate thermostability ■ High regio- and enantioselectivity ■ NADPH-dependent ■ Liquid / formulation with glycerin Comment: For quality assurance AB503595 is tested against benzylacetone as standard substrate at 30°C and pH 8.5. Examples of chiral products obtained from reactions catalyzed by AB503595 with isolated enzyme or whole cell systems: O O Me O O O O Cl ee 97% ee 98% AB503596 – CAS 156621-13-5 Pseudomonas putida Monooxygenase, bacterial, recombinant from E. Coli Properties: ■ Baeyer-Villiger-Oxidation of aromatic ketones ■ Able to perform sulfur oxidations ■ High regio- and enantioselectivity ■ NADPH-dependent ■ Liquid / formulation with glycerin Comment: For quality assurance AB503596 is tested against 4-Hydroxyacetophenone as standard substrate at 30°C and pH 8.5. Examples of chiral products obtained from reactions catalyzed by AB503596 with isolated enzyme or whole cell systems: O O O OMe O O O S ee 99% ee 99% abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com H N
30 AB503597 – CAS 156621-13-5 Pseudomonas fluorescens Monooxygenase, bacterial, recombinant from E. Coli Properties: ■ Baeyer-Villiger-Oxidation of aromatic ketones ■ Able to perform sulfur oxidations ■ High regio- and enantioselectivity ■ NADPH-dependent ■ Liquid / formulation with glycerin Comment: For quality assurance AB503597 is tested against 4-Hydroxyacetophenone as standard substrate at 30°C and pH 8.5. Examples of substrates converted by AB503597: O H N O O O O OH AB503598 – CAS 941741-04-4 Pseudomonas veronii Monooxygenase, bacterial, recombinant from E. Coli Properties: ■ Baeyer-Villiger-Oxidation of linear ketones ■ High regio- and enantioselectivity ■ NADPH-dependent ■ Liquid / formulation with glycerin Comment: For quality assurance AB503598 is tested against 4-Decanone as standard substrate at 30°C and pH 8.5. Examples of Substrates converted by AB503598: O O O Gute Chemie
Gute Chemie. Baeyer-Villiger Monooxygenases (BVMOs) 31 Baeyer-Villiger Monooxygenases Kit AB503599 Baeyer-Villiger-Monooxygenases screening kit, bacterial, recombinant from E.Coli, contains all six bacterial BVMOs as liquid formulations with glycerin (AB503593 - AB503598; 6 x 0.5ml) ■ Liquid / formulation with glycerin Chiral products can be obtained from reactions catalyzed by Baeyer-Villiger Monooxygenases with isolated enzyme or whole cell systems: AB506076 (5S)-5-Methyloxepan-2-one 116836-72-7 AB506077 (4S)-4-(3-Methoxybenzyl)-oxolan-2-one 171230-53-8 AB506078 (1S)-1-(3-Methoxyphenyl)-eth-1-yl acetate 1007894-87-2 AB506079 (S)-Methyl phenylsulfoxide 18453-46-8 O O O O O O O S O O Bulk amounts available. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
32 Gute Chemie
Gute Chemie. Amine Transaminases 33 Gute Chemie. Amine Transaminases Amine transaminases catalyze the transfer of an amino group from a primary amine to a prochiral ketone (or aldehyde). Amine transaminases are highly enantioselective and therefore can be used for the resolution of racemic amines or the synthesis of chiral amines from inexpensive ketones. Example of chiral resolution: O NH2 NH2 R3 R4 R3 R4 O NH2 R1 R2 R1 R2 + R1 R2 Example of asymmetric synthesis: NH2 O O R3 R4 R3 R4 R1 R2 NH2 R1 R2 ATAs are pyridoxal-5‘-phosphate dependent enzymes and their substrate range includes alkyl and aromatic amines, amino acids, amino esters and amino alcohols. Typical amine donors are: alanine, ethylamine, 1- and 2-propylamine, 1- and 2-butylamine and others. The „Enzymicals recombinant microbial expression platform“ ensures stable quality and easy production scale-up. Final formulation can be adapted to meet the production process requirements. References & Futher Information Höhne, M., Bornscheuer, U.T. , Biocatalytic routes to optically active amines, ChemCatChem, 1, 42-51, (2009). abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
34 AB503600 Aspergillus fumigatus Transaminase, eukaryotic, recombinant from E. Coli 9030-47-1 AB503601 Gibberella zeae Transaminase, eukaryotic, recombinant from E. Coli 9030-47-1 AB503602 Neosartorya fischeri Transaminase, eukaryotic, recombinant from E. Coli 9030-47-1 AB503603 Aspergillus oryzae Transaminase, eukaryotic, recombinant from E. Coli 9030-47-1 AB503604 Aspergillus terreus Transaminase, eukaryotic, recombinant from E. Coli 9030-47-1 AB503605 Penicillium chrysogenum Transaminase, eukaryotic, recombinant from E. Coli 9030-47-1 AB503606 Mycobacterium vanbaalenii Transaminase, bacterial, recombinant from E. Coli 9030-47-1 AB503607 Silicibacter pomeroyi Transaminase, bacterial, recombinant from E. Coli 9030-47-1 AB503608 Amin transaminases screening kit, recombinant from E.Coli, contains all eight ATAs (AB503600 - AB503607; 8 x 50mg) ■ For asymmetric synthesis of chiral amines from ketones Gute Chemie
Gute Chemie. Amine Transaminases 35 Properties: ■ AB503600 - AB503606 strictly (R)-selective ■ AB503607 strictly (S)-selective ■ Conversion of aliphatic, arylaliphatic and aromatic ketones ■ Solid / lyophilized powder Comment: For quality assurance AB503600 - AB503606 are tested against (R)-1-phenylethanamine at pH 7.5 and AB503607 against (S)-1-phenylethanamine as standard substrate at pH 9.5 and 25°C. Chiral products can be obtained by asymmetric synthesis catalyzed by ATAs: AB506080 (R)-2-Aminopentane 33985-20-5 NH2 AB389004 (R)-4-(3-Amino-butyl)-phenol 115548-15-7 NH2 HO Bulk amounts available. “Ready to use“ screening kit and more ATAs are available upon request. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
36 Gute Chemie
Gute Chemie. Imine Reductases (IREDs) 37 Gute Chemie. Imine Reductases (IREDs) Enzymatic asymmetric imine reduction is a promising alternative for the synthesis of chiral amines. Imine re- ductases (IREDs) catalyze the reduction of imines to amines by using NAD(P)H as a hydride source. These en- zymes are classified as EC 1.5.1.48, alongside other enzymes with imine-forming and imine-reducing activity. IRED N R1 NAD(P)H NAD(P)* N H R1 The transformation of prochiral imines to chiral amines using IREDs offer a quantitative asymmetric route to amine products of high optical purity. So these enzymes can have a valuable complementary role to play in chiral amine synthesis. References & Futher Information Gamenara, U. and Domínguez de María, P., Enantioselective imine reduction catalyzed by imine reductases and artificial metalloenzymes, Organic & Biomolecular Chemistry, 2014,12, 2989-2992 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
38 AB503611 Streptomyces sp. GF3587 Imine Reductase, bacterial, recombinant from E.Coli AB503613 Streptomyces sp. GF3546 Imine Reductase, bacterial, recombinant from E.Coli AB503614 Paenibacillus eldii B69 Imine Reductase, bacterial, recombinant from E.Coli AB589397 Nocardia cyriacigeorgica Imine Reductase, bacterial, recombinant from E.Coli AB503615 IRED screening kit, recombinant from E.Coli, contains 4x0.5ml IREDs as liquid formulations with glycerin; AB503611, AB503613, AB503614, AB589397 Properties: ■ Accept cyclic and acyclic substrates ■ AB503611 and AB589397 are (R)-selective towards the standard substrate 2-Methyl-1-pyrroline ■ AB503613 and AB503614 are (S)-selective towards the standard substrate 2-Methyl-1-pyrroline ■ Liquid / formulation with glycerin Comment: For quantitative assurance IREDs are tested against 2-Methyl-1-pyrroline as standard substrate at pH 7.5 in the presence of NADPH. Gute Chemie
Gute Chemie. Imine Reductases (IREDs) 39 Examples of chiral products obtained by asymmetric reduction catalyzed by IREDs: N H ee 99% N H ee 99% N H ee 99% Examples of substrates converted by IREDs: N H N H NH Bulk amounts available. Mutants with changed cofactor specificity are available upon request. abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
40 Gute Chemie
Gute Chemie. Halohydrin Dehalogenases (HHDHs) 41 Gute Chemie. Halohydrin Dehalogenases (HHDHs) Halohydrin dehalogenases are enzymes that convert vicinal halohydrins to an epoxide, a halide ion, and a proton. The conversions catalyzed by halohydrin dehalogenases are reversible, depending on the nature of the leaving group. In the reverse (epoxide-ring opening) reaction various alternative negatively charged nucleophi- les can be accepted, such as cyanide and azide. Thus a wide range of reactions can be carried out. Example of the catalytic scope of halohydrin dehalogenase-catalyzed epoxide-ring opening of 1,2-epoxybutane and various nucleophiles: OH R N3 - N3 OH + OH R R OH CN R CN- R R - NO2 O O X- NO2 H2O OH OH R ONO OH R X X- = Cl-, Br-, I- HCOO- OH R OCHO OCN- O O NH R SCN- OH R SCN Thus, products of this enzymatic reactions are enantiomerically pure compounds (a chiral epoxide and a chiral beta-substituted Alcohol) which can be used as chiral building blocks for the production of a wide range of chemicals. Final formulation can be adapted to meet the production process requirements. References & Futher Information Zhong-Yu You et al, Properties and biotechnological applications of halohydrin dehalogenases: current state and future perspectives, Applied Microbiology and Biotechnology, 2013, 97 (1), pp 9-21 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
42 AB503616 Tistrella mobilis Halohydrin-dehalogenase, bacterial, recombinant from E.Coli 402819-12-9 AB503617 Marine metagenome Halohydrin-dehalogenase, bacterial, recombinant from E.Coli 402819-13-0 AB503618 Methylibium petroleiphilum Halohydrin-dehalogenase, recombinant from E.Coli 402819-13-0 AB503619 Marine metagenome Halohydrin-dehalogenase, bacterial, recombinant from E.Coli 402819-13-0 AB503620 Thauera sp. Halohydrin-dehalogenase, bacterial, recombinant from E. Coli 402819-13-0 AB503621 Marine metagenome Halohydrin-dehalogenase, bacterial, recombinant from E.Coli 402819-13-0 AB503622 Gamma proteobacterium halohydrin-dehalogenase, bacterial, recombinant from E.Coli 402819-12-9 AB503623 Parvibaculum lavamentivorans halohydrin-dehalogenase, bacterial, recombinant from E.Coli AB503624 Uncultured bacterium halohydrin dehalogenase, bacterial, recombinant from E.Coli AB503625 Halohydrin dehalogenases screening kit, recombinant from E. Coli, contains all nine Halohydrin dehalogenases (AB503616 - AB503524; 9 x 50mg) ■ For fast investigation and screening of substrate scope Bulk amounts available. “Ready to use“ screening kit and more HHDHs are available upon request. Gute Chemie
Gute Chemie. Halohydrin Dehalogenases (HHDHs) 43 Properties: ■ Catalytic tool box for the evaluation of synthesis routes ■ Reversible dehalogenation of beta-haloalcohols under epoxide formation ■ Formation of novel carbon-carbon, carbon-nitrogen, or carbon-oxygen bonds ■ Promiscuous epoxide ring-opening activity ■ Cyanide, azide, or nitrite are accepted as nucleophiles ■ Solid / lyophilized powder Comment: For quality assurance HHDH01-09 are tested against 1,3-Dichloro-2-propanol as standard substrate at pH 8.2 and 30°C. Examples for HHDH catalyzed products can be: AB513981 (2R)-1-Azido-2-butanol 1111072-58-2 AB513982 (3R)-3-Hydroxypentanenitrile 198561-27-2 AB513983 (2R)-1-Chloro-2-butanol 185033-57-2 AB513984 (2R)-1-Bromo-2-butanol 117365-09-0 AB513985 (2R)-1-Iodo-2-butanol 844486-96-0 AB513986 (5R)-5-Ethyl-2-oxazolidinone 947683-08-1 OH N3 OH N OH OH OH Cl Br I O O NH abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
44 Gute Chemie
Gute Chemie. Phosphotransferases 45 Gute Chemie. Phosphotransferases Phosphotransferases (EC 2.7) catalyze the transfer of phosphate groups from phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the substrate gains a phosphate group and a specific donor molecule provides a phosphate group. ATP ADP XH R O X R P OH HO R-X-: R'-COO-, R'-O-, R'-NH- The sub-category phosphotransferase is divided up in categories based on the type of group that accepts the transfer. Groups that are classified as phosphate acceptors include: alcohols, carboxy groups and nitrogenous groups. Important constituents of this subclass of transferases are various kinases which are types of phos- photransferases that transfer a phosphate group from ATP to a substrate. AB503627 Limulus Polyphemus Arginine-Kinase, bacterial, recombinant from E.Coli ■ Catalyzes the synthesis of N(omega)-phospho-L-arginine using ATP as donor ■ Liquid / formulation with glycerin 9026-70-4 AB503628 Brucella abortus Erythritol-Kinase, bacterial, recombinant from E.Coli ■ Catalyzes the synthesis of D-erythritol 4-phosphate using ATP as donor ■ Liquid / formulation with glycerin 9030-64-2 AB503629 E.Coli Shikimat-Kinase, bacterial, recombinant from E.Coli ■ Catalyzes the synthesis of shikimate 3-phosphate using ATP as donor ■ Liquid / formulation with glycerin 9031-51-0 Comment: For quality assurance AB503627 - AB503629 are tested against their corresponding standard substrate at pH 7.5 and 25°C by the use of a coupled enzymatic assay system with phosphoenolpyruvate, pyruvatkinase and lactatdehydrogenase and photometric measurement of NADH consumption. Robust standard operation procedures are provided with each delivery. References & Futher Information Biocatalytic Phosphorylation of Metabolites. Dominik Gauss, Bernhard Schönenberger, Getachew S. Molla, Birhanu M. Kinfu, Jennifer Chow,, Andreas Liese, Wolfgang R. Streit, and Roland Wohlgemuth in Applied Biocatalysis: From Fundamental Science to Industrial Applications WILEY-VCH (2016) abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
46 Gute Chemie
Gute Chemie. Selected Chiral Compounds 47 Gute Chemie. Selected Chiral Compounds AB475825 (1S,6R)-6-(Methoxycarbonyl)cyclohex-3- ene-1-carboxylic acid 88335-94-8 AB475827 (2S,4R)-4-Amino-1-phenylpentan-2-ol 1787253-31-9 AB504643 (R)-1-(1-Adamantyl)ethanamine 887336-05-2 H O O OH O OH NH2 AB504644 (S)-1-(1-Adamantyl)ethanamine 887336-06-3 AB506059 (1R,2S,4S,5S)-Methyl 4-hydroxy-7-oxo-6- oxabicyclo[3.2.1]octane-2-carboxylate; 95%, ee 99% 121787-41-5 H H NH2 H H H NH2 O O HO O O AB506060 cis-9,10-Epoxystearic acid 24560-98-3 H O H O OH abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
48 Gute Chemie. Chiral bis(oxazoline) derivatives (BOX) for catalytic applications abcr provides a series of bis(oxazoline) compounds („BOX“) which could be applied as ligands in a wide varie- ty of enantioselective reactions. The excellent enantioselectivities show their enormous potential for synthe- tic procedures giving access to new structural motifs. R1 ZnCl F F + Br R2 N R2 R2 (DME)NiCl2 (5 mol-%) (S,S)-ligand (6 mol-%) (DME)NiC (S,S)-ligan R) (6 mol-%) ) T#$%& '()* ,.) THF, 0°C THF, 0° R1 „Nickel-Catalyzed Negishi Cross-Coupling of Bromodifluoroacetamides.“ A. Tarui, S. Shinohara, K. Sato, M. Omote, A. Ando, Organic Letters, 2016, 18(5), 1128-1131. / up to 94% yield up to 94% yiel F F R2 N 0 0 R2 N N / Ph (S,S)-ligand Ph R1 ZnCl X + F3C (DME)NiC (S,S)-ligand (8 mol-% (DME)NiCl2 (6 mol-%) (S,S)-ligand (8 mol-%) ) alkyl alkyl THF, diglyme THF, diglyme C - ! alkyl CF3 R ) R1 " " N N Ph (S,S)-ligand Ph „Stereoconvergent Negishi Arylations of Racemic Secondary Alkyl Electrophiles: Differentiating between a CF and an Alkyl Group.“ 3 Y. Liang, G. C. Fu, Journal of the American Chemical Society, 2015, 137(30), 9523-9526. 2R S? NH H N ? (R,R)-Catalyst (35 mol-%) Mn (R,R)-Catalyst (35 mol-%) ) 2 1 45 6789: ;< 3 2 =1 4> 678 PhCF3, 115 °C, 24 h up to 86% yield up to 98% ee (S) isomer ) H N 2R S? N ? @ @ N N Cu Ph Ph AB@ @AB (R,R)-Catalyst „Copper(II)-Catalyzed Enantioselective Intramolecular Cyclization of N-Alkenylureas.“ S. Fu, H. Yang, G. Li, Y. Deng, H. Jiang, W. Zeng, Organic Letters 2015, 17(4), 1018-1021. Br RD alkyl D Co (S,S)-ligand (12 mol-%) CoI2 (10 mol-%) (S,S)-ligand (12 mol-%) (S,S)-ligand (12 mol-%) + ArylMgBr ArylMgBr THF, -80° THF, -80°C up to 96% yiel up to 97% ee (S) isomer up to 96% yield up to 97% ee (S) isomer up to 97% ee (S) isomer Aryl RD alkyl D E E N N Bn (S,S)-ligand Bn „Cobalt-Bisoxazoline-Catalyzed Asymmetric Kumada Cross-Coupling of Racemic α-Bromo Esters with Aryl Grignard Reagents.“ J. Mao, F. Liu, M. Wang, L. Wu, B. Zheng, S. Liu, J. Zhong, Q. Bian, P. J. Walsh, Journal of the American Chemical Society, 2014, 136(50), 17662-17668. Gute Chemie
Gute Chemie. Chiral bis(oxazoline) derivatives (BOX) 49 N N N N N N N N O O O O O O O O AB 171403 AB 150033 AB 331792 AB 137494 N N N N O O O O N N N N O O O O AB 471844 AB 471845 AB 471846 AB 471847 N N N N N N N N O O O O O O O O AB 471848 AB 471849 AB 471850 AB 471851 N N N N O O O O N N N N O O O O AB 471852 AB 471853 AB 471854 AB 471855 abcr GmbH ▪ Phone +49 721 95061 - 0 ▪ Fax +49 721 95061 - 80 ▪ info@abcr.com ▪ www.abcr.com
50 Gute Chemie. Notes. Gute Chemie
Publishing details abcr GmbH Im Schlehert 10 76187 Karlsruhe Germany Phone +49 721 95061 - 0 Fax +49 721 95061 - 80 info@abcr.com ▪ www.abcr.com Registered office Karlsruhe Managing Director Dr. Jan Schuricht District court AG Mannheim HRB 104793 Tax number 35005/14749 VAT number DE 815518524 DUNS number 320054844 Publisher: abcr GmbH 513938.0618.3-23 © abcr - All rights reserved.
Gute Chemie. Greater diversity, choice and value. Make use of our e-papers to quickly and easily browse through our catalogues and flyers and search for products. All products listed in the e-papers are linked to the respective product detail page within our website where you will find further information. We can also send the catalogues and flyers by mail. Palladium Catalysts Life Science Drug Design Silicon Compounds Organozinc Reagents Fluorinated Compounds Aryne Precursors Freaky Amino Acids Catalysts Ligands Find 400,000 specialty chemicals in our webshop www.abcr.com abcr GmbH Germany +49 721 95061-0 info@abcr.com abcr swiss AG +41 41 7201882 info@abcr-swiss.ch abcr france SAS +33 4 7291 3100 info@abcr-france.fr abcr IRL Ltd. +353 56 7738971 info@abcr-irl.ie abcr UK Ltd. +44 161 8187062 info@abcr-uk.com LLC ABCR CHEMI RUS +7 495 9664181 info@abcr-russia.ru Life ScienceNew Chirals for Drug DesignNNNN01Life ScienceNew Chirals for Drug DesignNNNN01New Organozinc Reagents for Organic Synthesis01New Organozinc Reagents for Organic Synthesis01Palladium catalysts for C-C and C-N coupling reactions01Palladium catalysts for C-C and C-N coupling reactions01Commercial Organofunctional Silanes for Diagnostics and Separation01Commercial Organofunctional Silanes for Diagnostics and Separation0101Available in bulk quantities Fluoro Organic Intermediates01Available in bulk quantities Fluoro Organic Intermediates(R,R)-Catalyst (35 mol-%)MnO2 (3 eq.), Li2CO3 (2 eq.)PhCF3, 115 °C, 24 hup to 86% yield) (2 eq.)NNOSO2RHHNNHSO2Rup to 94% yield(S,S)-ligand (8 mol-%)THF, diglyme-20°CRalkylNN)(S,S)-ligand (8 mol-%)R1CF3R1+F3C(S,S)-ligand (8 mol-%THF, diglym-20°alkylCoI2 (10 mol-%)(S,S)-ligand (12 mol-%)THF, -80°CArylMgBrROup to 96% yield)ROArylalkylCo(S,S)-ligand (12 mol-%THF, -80°CROBralkyl+ArylMgBrup to 96% yieldONNOCuTfOOTfNNO(R,R)-Catalyst (35 mol-%)MnO2 (3 eq.), Li2CO3 (2 eq.)PhCF3, 115 °C, 24 hup to 86% yield) (2 eq.)NNOSO2RHHNNHSO2RR2(DME)NiCl2 (5 mol-%)(S,S)-ligand (6 mol-%)TMEDA (1.6 eq.)THF, 0°Cup to 94% yieldR (5 mol-%) (6 mol-%)R1FFNOR2R2ZnClR1+BrFFNOR2R2(DME)NiCl(S,S)-ligandTMEDA (1.6 eq.)THF, 0°Cup to 94% yield(DME)NiCl2 (6 mol-%)(S,S)-ligand (8 mol-%)THF, diglyme-20°CRalkylONNO)(S,S)-ligand (8 mol-%)R1alkylCF3ZnClR1+F3C(DME)NiCl(S,S)-ligand (8 mol-%THF, diglym-20°XalkylCoI2 (10 mol-%)(S,S)-ligand (12 mol-%)THF, -80°CArylMgBrROup to 96% yield)ROArylalkylCo(S,S)-ligand (12 mol-%THF, -80°CROBralkyl+ArylMgBrup to 96% yieldNNO(S,S)-ligandONNOCuTfOOTfNNOCO2RArORArOCONR2OR1R2ArRNNNRONRNNR2R1NNRTsNR1R2R1CO2R2ONR1R2R3NR1R2R3OORetc.OTfTMSCsFCO2RArORArOCONR2OR1R2ArRNNNRONRNNR2R1NNRTsNR1R2R1CO2R2ONR1R2R3NR1R2R3OORetc.MeCNrt