- Dual Mechanoenzymatic Kinetic Resolution of (±)-Ketorolac
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Recently, biocatalysis mediated by mechanical energy has become a convenient strategy to obtain highly valuable products following the principles of green chemistry. In particular, mechanoenzymatic techniques have allowed the isolation of chiral drugs wit
- Juaristi, Eusebio,Pérez-Venegas, Mario,Rodríguez-Trevi?o, Agustín Mario
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- A synthetic protocol for (?)-ketorolac; development of asymmetric gold(I)-catalyzed cyclization of allyl alcohol with pyrrole ring core
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An asymmetric synthesis of (?)- and (+)-ketorolac was achieved with 89% ee using a novel Friedel–Crafts (FC) type C–C bond forming cyclization of an allyl alcohol containing a pyrrole ring core in the presence of a bimetallic gold(I) salt complex prepared from a 2:2:1 combination of AuCl·SMe2, AgOTf and chiral Quinaphos.
- Sasaki, Ikuo,Yamasaki, Naoto,Kasai, Yusuke,Imagawa, Hiroshi,Yamamoto, Hirofumi
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supporting information
(2020/01/13)
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- Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
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A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.
- Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
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p. 1067 - 1078
(2018/08/01)
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- Synthesis of diastereomeric anhydrides of (RS)-ketorolac and (RS)-etodolac, semi-preparative HPLC enantioseparation, establishment of molecular asymmetry and recovery of pure enantiomers
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Herein, enantioseparation of two anti-inflammatory drugs, namely, (RS)-ketorolac and (RS)-etodolac, commonly marketed and administered as racemates, was achieved by RP-HPLC. This method provided very low limit of detection values (3.69 and 3.02 ng mL-1 for diastereomeric derivatives of (R)- and (S)-Ket, respectively) as compared to those reported in literature. (S)-Naproxen benzotriazole ester, which was used as a chiral reagent, was synthesized and characterized by UV, IR, and 1H NMR spectroscopies, elemental analysis, and polarimetry. The diastereomeric derivatives were synthesized via microwave irradiation, separated on an analytical scale by RP-HPLC, and then isolated by preparative HPLC. The use of a mobile phase containing methanol and aqueous triethylamine phosphate (TEAP) in the isocratic mode was found to be successful for the separation of diastereomeric derivatives, and the separation conditions with respect to pH, flow rate, and buffer concentration were optimized. The diastereomeric derivatives were characterized, and their absolute configuration was established. Hydrolysis of the derivatives provided native enantiomers under mild reaction conditions. This study describes the successful enantioseparation of the above mentioned two analytes by semi-preparative HPLC with easy recovery of the native enantiomers without racemization and with the establishment of molecular asymmetry.
- Malik, Poonam,Bhushan, Ravi
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p. 13681 - 13691
(2017/11/27)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 54
(2010/12/31)
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- Development of new HPLC chiral stationary phases based on native and derivatized cyclofructans
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An unusual class of chiral selectors, cyclofructans, is introduced for the first time as bonded chiral stationary phases. Compared to native cyclofructans (CFs), which have rather limited capabilities as chiral selectors, aliphatic-and aromatic-functionalized CF6s possess unique and very different enantiomeric selectivities. Indeed, they are shown to separate a very broad range of racemic compounds. In particular, aliphatic-derivatized CF6s with a low substitution degree baseline separate all tested chiral primary amines. It appears that partial derivatization on the CF6 molecule disrupts the molecular internal hydrogen bonding, thereby making the core of the molecule more accessible. In contrast, highly aromaticfunctionalized CF6 stationary phases lose most of the enantioselective capabilities toward primary amines, however they gain broad selectivity for most other types of analytes. This class of stationary phases also demonstrates high "loadability" and therefore has great potential for preparative separations. The variations in enantiomeric selectivity often can be correlated with distinct structural features of the selector. The separations occur predominantly in the presence of organic solvents.
- Sun, Ping,Wang, Chunlei,Breitbach, Zachary S.,Zhang, Ying,Armstrong, Daniel W.
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experimental part
p. 10215 - 10226
(2010/05/01)
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- Scope and mechanism of direct indole and pyrrole couplings adjacent to carbonyl compounds: Total synthesis of acremoauxin A and oxazinin 3
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Full details are provided for a recently invented method to couple indoles and pyrroles to carbonyl compounds. The reaction is ideally suited for structurally complex substrates and exhibits high levels of chemoselectivity (functional group tolerability), regioselectivity (coupling occurs exclusively at C-3 of indole or C-2 of pyrrole), stereoselectivity (substrate control), and practicality (amenable to scaleup). In addition, quaternary stereocenters are easily and predictably generated. The reaction has been applied to a number of synthetic problems including total syntheses of members of the hapalindole family of natural products, ketorolac, acremoauxin A, and oxazinin 3. Mechanistically, this coupling protocol appears to operate by a single electron-transfer process requiring generation of an electron-deficient radical adjacent to a carbonyl which is then intercepted by an indole or pyrrole anion.
- Richter, Jeremy M.,Whitefield, Brandon W.,Maimone, Thomas J.,Lin, David W.,Castroviejo, M. Pilar,Baran, Phil S.
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p. 12857 - 12869
(2008/09/16)
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- Direct coupling of pyrroles with carbonyl compounds: Short enantioselective synthesis of (S)-ketorolac
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An odd couple: The union of pyrroles and carbonyl compounds (ketones, amides, esters, lactones, lactams, see scheme) is described, and by the use of an intramolecular variant of this new method, the nonsteroidal, anti-inflammatory drug (S)-ketorolac has b
- Baran, Phil S.,Richter, Jeremy M.,Lin, David W.
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p. 609 - 612
(2007/10/03)
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- Enzymatic kinetic resolution of ketorolac
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Ketorolac 1 was resolved into each enantiomer by interesterification using lipase B from Candida antarctica. The acid reacted with various alcohols and the ester and acid were resolved up to >99% e.e. when reacted with octanol, which was the best result.
- Kim, Young Hee,Cheong, Chan Seong,Lee, So Ha,Kim, Kwan Soo
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p. 1865 - 1869
(2007/10/03)
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- Absolute Configuration of (-)-5-Benzoyl-1,2-dihydro-3H-pyrroloa>pyrrole-1-carboxylic Acid, the Active Enantiomer of Ketorolac
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The (-)-S isomer of 5-benzoyl-1,2-dihydro-3H-pyrroloa>pyrrole-1-carboxylic acid (1) is about 60 times more potent than the (+)-R isomer in the carrageenan edema test and ca. 230 times more active than the (+)-R isomer in the mouse phenylquinone writhing assay.
- Guzman, Angel,Yuste, Francisco,Toscano, Ruben A.,Young, John M.,Horn, Albert R. Van,Muchowski, Joseph M.
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p. 589 - 591
(2007/10/02)
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