In situ evaluation of kinetic resolution catalysts for nitroaldol by rationally designed fluorescence probe.

Development of effective chemical catalysts is a key concern in organic chemistry. Therefore, convenient screening systems for chemical catalysts are required, and although some fluorescence-based HTS systems have been developed, little attempt has been made to apply them to asymmetric catalysts. Therefore, we tried to develop a chiral fluorescence probe which can evaluate the reactivity and enantioselectivity of asymmetric catalysts. We focused on kinetic resolution catalysts as a target of our novel fluorescence probe, employing β-elimination following acylation of nitroaldol. Once the hydroxyl group of nitroaldol is acylated, β-elimination occurs immediately, affording nitro olefin. Therefore, we designed and synthesized a fluorescence probe with an asymmetric nitroaldol moiety. Its fluorescence intensity decreases dramatically upon β-elimination, so the fluorescence decrease is an indicator of the reaction yield. Thus, the enantioselectivity of kinetic resolution catalysts can be assessed simply by measuring the fluorescence intensities of the reaction mixtures of the two enantiomers; it is not necessary to purify the product. This fluorescence probe revealed that benzotetramisole is a superior catalyst for kinetic resolution of nitroaldol. Furthermore, we established an HTS system for asymmetric catalysts, using a fluorescence probe and benzotetramisole. To our knowledge, this is the first fluorescence-based HTS system for asymmetric catalysts.

[1]  Shasha Liu,et al.  3,6-Disubstituted carbazole-based bisboronic acids with unusual fluorescence transduction as enantioselective fluorescent chemosensors for tartaric acid. , 2009, The Journal of organic chemistry.

[2]  T. Arai,et al.  Direct monitoring of the asymmetric induction of solid-phase catalysis using circular dichroism: diamine-Cu(I)-catalyzed asymmetric Henry reaction. , 2006, Angewandte Chemie.

[3]  M. Finn,et al.  Use of a racemic derivatizing agent for measurement of enantiomeric excess by circular dichroism spectroscopy , 2001 .

[4]  Christian Wolf,et al.  A high-throughput screening protocol for fast evaluation of enantioselective catalysts. , 2002, The Journal of organic chemistry.

[5]  S. Matsunaga,et al.  Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution. , 2006, Journal of the American Chemical Society.

[6]  N. Kumagai,et al.  anti-Selective catalytic asymmetric nitroaldol reaction via a heterobimetallic heterogeneous catalyst. , 2009, Journal of the American Chemical Society.

[7]  Alain Wagner,et al.  High-throughput screening of enantioselective catalysts by immunoassay. , 2002, Angewandte Chemie.

[8]  Yasuteru Urano,et al.  Extension of the applicable range of fluorescein: a fluorescein-based probe for Western blot analysis. , 2005, Angewandte Chemie.

[9]  F. Tanaka,et al.  Design and use of fluorogenic aldehydes for monitoring the progress of aldehyde transformations. , 2004, Journal of the American Chemical Society.

[10]  Scott J. Miller,et al.  Selection of enantioselective acyl transfer catalysts from a pooled peptide library through a fluorescence-based activity assay: an approach to kinetic resolution of secondary alcohols of broad structural scope. , 2001, Journal of the American Chemical Society.

[11]  Y. Urano,et al.  Highly efficient and photostable photosensitizer based on BODIPY chromophore. , 2005, Journal of the American Chemical Society.

[12]  Y. Urano,et al.  Design and synthesis of a library of BODIPY-based environmental polarity sensors utilizing photoinduced electron-transfer-controlled fluorescence ON/OFF switching. , 2007, Journal of the American Chemical Society.

[13]  Scott J. Miller,et al.  A Chemosensor-Based Approach to Catalyst Discovery in Solution and on Solid Support , 1999 .

[14]  K. Hult,et al.  High-throughput enzymatic method for enantiomeric excess determination of O-acetylated cyanohydrins. , 2006, Journal of the American Chemical Society.

[15]  K. Ohkubo,et al.  Rational principles for modulating fluorescence properties of fluorescein. , 2004, Journal of the American Chemical Society.

[16]  S. Stauffer,et al.  Fluorescence resonance energy transfer (FRET) as a high-throughput assay for coupling reactions. Arylation of amines as a case study. , 2003, Journal of the American Chemical Society.

[17]  M. Finn,et al.  Discovery and characterization of catalysts for azide-alkyne cycloaddition by fluorescence quenching. , 2004, Journal of the American Chemical Society.

[18]  C. Sih,et al.  Quantitative analyses of biochemical kinetic resolutions of enantiomers , 1982 .

[19]  Tsuyoshi Inoue,et al.  Improving the Quality of Protein Crystals Using Stirring Crystallization , 2004 .

[20]  Kevin Burgess,et al.  BODIPY dyes and their derivatives: syntheses and spectroscopic properties. , 2007, Chemical reviews.

[21]  F. A. Luzzio,et al.  The Henry reaction: recent examples , 2001 .

[22]  Yasuteru Urano,et al.  Highly sensitive fluorescence probes for nitric oxide based on boron dipyrromethene chromophore-rational design of potentially useful bioimaging fluorescence probe. , 2004, Journal of the American Chemical Society.

[23]  J. Morken,et al.  Thermographic selection of effective catalysts from an encoded polymer-bound library , 1998, Science.

[24]  Masashi Yoshimura,et al.  Application of a Stirring Method to Micro-Scale and Vapor Diffusion Protein Crystallization , 2003 .

[25]  D. Díaz,et al.  Measurement of enantiomeric excess of amines by mass spectrometry following kinetic resolution with solid-phase chiral acylating agents , 2001 .

[26]  L. Pu,et al.  A cyclohexyl-1,2-diamine-derived bis(binaphthyl) macrocycle: enhanced sensitivity and enantioselectivity in the fluorescent recognition of mandelic acid. , 2005, Angewandte Chemie.

[27]  S. Matsunaga,et al.  Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution , 2009 .

[28]  Y. Nishida,et al.  On-line HPLC−Exciton CD Analysis Using a Chiral Benzoyl Agent, (S)-TBMB Carboxylic Acid: A Promising Approach toward Selective Identification of Enantiomeric Diols and Diamines , 1997 .

[29]  Manfred T Reetz,et al.  A Method for High-Throughput Screening of Enantioselective Catalysts. , 1999, Angewandte Chemie.

[30]  Scott J. Miller,et al.  Nucleophilic chiral amines as catalysts in asymmetric synthesis. , 2003, Chemical reviews.

[31]  Manfred T Reetz,et al.  New methods for the high-throughput screening of enantioselective catalysts and biocatalysts. , 2002, Angewandte Chemie.

[32]  Detlev Belder,et al.  Super-High-Throughput Screening of Enantioselective Catalysts by Using Capillary Array Electrophoresis. , 2000, Angewandte Chemie.

[33]  Y. Onda,et al.  Kinetic Resolution of Racemic Carboxylic Acids Using Achiral Alcohols by the Promotion of Benzoic Anhydrides and Tetramisole Derivatives: Production of Chiral Nonsteroidal Anti-Inflammatory Drugs and Their Esters , 2008 .

[34]  C. Seto,et al.  Using a lipase as a high-throughput screening method for measuring the enantiomeric excess of allylic acetates. , 2003, The Journal of organic chemistry.

[35]  Scott J. Miller,et al.  A Polymeric and Fluorescent Gel for Combinatorial Screening of Catalysts , 2000 .

[36]  F. Tanaka,et al.  A fluorogenic aldehyde bearing a 1,2,3-triazole moiety for monitoring the progress of aldol reactions. , 2009, The Journal of organic chemistry.

[37]  S. Matsunaga,et al.  A heterobimetallic Pd/La/Schiff base complex for anti-selective catalytic asymmetric nitroaldol reactions and applications to short syntheses of beta-adrenoceptor agonists. , 2008, Angewandte Chemie.

[38]  A. P. Silva,et al.  Fluorescent PET(Photoinduced Electron Transfer) reagents for thiols , 1998 .

[39]  Eric V Anslyn,et al.  Transitioning enantioselective indicator displacement assays for alpha-amino acids to protocols amenable to high-throughput screening. , 2008, Journal of the American Chemical Society.

[40]  Michael A Evans,et al.  Isotopically chiral probes for in situ high-throughput asymmetric reaction analysis. , 2002, Journal of the American Chemical Society.

[41]  Lin Pu,et al.  Fluorescence of organic molecules in chiral recognition. , 2004, Chemical reviews.

[42]  C. Palomo,et al.  Recent Advances in the Catalytic Asymmetric Nitroaldol (Henry) Reaction , 2007 .

[43]  Isamu Shiina,et al.  The first asymmetric esterification of free carboxylic acids with racemic alcohols using benzoic anhydrides and tetramisole derivatives: an application to the kinetic resolution of secondary benzylic alcohols , 2007 .

[44]  John F. Hartwig,et al.  A Fluorescence-Based Assay for High-Throughput Screening of Coupling Reactions. Application to Heck Chemistry , 1999 .

[45]  Qing Xu,et al.  Kinetic resolution of 2,2-difluoro-3-hydroxy-3-aryl-propionates catalyzed by organocatalyst (R)-benzotetramisole , 2008 .

[46]  S. Matsunaga,et al.  Stereodivergent catalytic doubly diastereoselective nitroaldol reactions using heterobimetallic complexes. , 2008, Organic letters.

[47]  E. Vedejs,et al.  Efficiency in nonenzymatic kinetic resolution. , 2005, Angewandte Chemie.

[48]  Qing Xu,et al.  Nonenzymatic kinetic resolution of racemic 2,2,2-trifluoro-1-aryl ethanol via enantioselective acylation , 2009 .

[49]  K. Mikami,et al.  Super High Throughput Screening (SHTS) of Chiral Ligands and Activators: Asymmetric Activation of Chiral Diol-Zinc Catalysts by Chiral Nitrogen Activators for the Enantioselective Addition of Diethylzinc to Aldehydes. , 1999, Angewandte Chemie.

[50]  Y. Urano,et al.  Creation of superior carboxyfluorescein dyes by blocking donor-excited photoinduced electron transfer. , 2006, Organic letters.

[51]  Scott J. Miller,et al.  Proton-activated fluorescence as a tool for simultaneous screening of combinatorial chemical reactions. , 2002, Current opinion in chemical biology.

[52]  F. Tanaka,et al.  Rapid analysis of solvent effects on enamine formation by fluorescence: how might enzymes facilitate enamine chemistry with primary amines? , 2004 .

[53]  J. Biellmann,et al.  Synthesis of 8-heteroatom-substituted 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene dyes (BODIPY) , 2006 .

[54]  F. Tanaka,et al.  Fluorescent detection of carbon-carbon bond formation. , 2003, Journal of the American Chemical Society.

[55]  M. Shair,et al.  Reaction microarrays: a method for rapidly determining the enantiomeric excess of thousands of samples. , 2001, Journal of the American Chemical Society.

[56]  V. B. Birman,et al.  Benzotetramisole: a remarkably enantioselective acyl transfer catalyst. , 2006, Organic letters.

[57]  V. Lynch,et al.  Using enantioselective indicator displacement assays to determine the enantiomeric excess of alpha-amino acids. , 2008, Journal of the American Chemical Society.