- Stereoselective Lewis base catalyzed formal 1,3-dipolar cycloaddition of azomethine imines with mixed anhydrides
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Stereoselective synthesis of pyrazolidinones via dipolar cycloaddition of azomethine imines with active esters under Lewis base catalysis is presented. The active esters are readily generated in situ from the corresponding acids. Products, which are obtai
- Hesping, Lena,Biswas, Anup,Daniliuc, Constantin G.,Mück-Lichtenfeld, Christian,Studer, Armido
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- Isothiourea-Catalysed Regioselective Acylative Kinetic Resolution of Axially Chiral Biaryl Diols
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An operationally simple isothiourea-catalysed acylative kinetic resolution of unprotected 1,1′-biaryl-2,2′-diol derivatives has been developed to allow access to axially chiral compounds in highly enantioenriched form (s values up to 190). Investigation of the reaction scope and limitations provided three key observations: i) the diol motif of the substrate was essential for good conversion and high s values; ii) the use of an α,α-disubstituted mixed anhydride (2,2-diphenylacetic pivalic anhydride) was critical to minimize diacylation and give high selectivity; iii) the presence of substituents in the 3,3′-positions of the diol hindered effective acylation. This final observation was exploited for the highly regioselective acylative kinetic resolution of unsymmetrical biaryl diol substrates bearing a single 3-substituent. Based on the key observations identified, acylation transition state models have been proposed to explain the atropselectivity of this kinetic resolution.
- Qu, Shen,Greenhalgh, Mark D.,Smith, Andrew D.
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supporting information
p. 2816 - 2823
(2019/02/05)
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- Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
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A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
- Huy, Peter H.,Mbouhom, Christelle
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p. 7399 - 7406
(2019/08/20)
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- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND/OR TRYPTOPHAN 2,3-DIOXYGENASE
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The present invention relates to compounds of Formula (I) inhibiting indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) enzymes. Further, their synthesis and their use as medicaments in inter alia cancer is disclosed.
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Page/Page column 113
(2019/03/05)
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- Protected pyrimidine nucleosides for cell-specific metabolic labeling of RNA
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RNA molecules can perform a myriad of functions, from the regulation of gene expression to providing the genetic blueprint for protein synthesis. Characterizing RNA expression dynamics, in a cell-specific manner, still remains a great challenge in biology. Herein we present a new set of protected alkynyl nucleosides for cell-specific metabolic labeling of RNA. We anticipate these analogs will find wide spread utility toward the goal of understanding RNA expression in complex cellular and tissue environments, even within living animals.
- Beasley, Samantha,Nguyen, Kim,Fazio, Michael,Spitale, Robert C.
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supporting information
p. 3912 - 3915
(2018/09/27)
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- One-pot electrochemical synthesis of acid anhydrides from alcohols
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One-pot indirect electrochemical oxidation of alcohols in the methylene chloride–aqueous solution of sodium hydrocarbonate two-phase system in the presence of potassium iodide, 4-acetylamino-2,2,6,6-tetramethylpiperidin-1-oxyl, and 2,6-lutidine results in
- Kashparova,Papina,Kashparov,Zhukova, I. Yu.,Ilchibaeva,Kagan, E. Sh.
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p. 2733 - 2735
(2017/12/26)
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- Enantioselective Synthesis of 3,5,6-Substituted Dihydropyranones and Dihydropyridinones using Isothiourea-Mediated Catalysis
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The scope of dihydropyranone and dihydropyridinone products accessible by isothiourea-catalyzed processes has been expanded and explored through the use of 2-N-tosyliminoacrylates and 2-aroylacrylates in a Michael addition-lactonization/lactamization cascade reaction. Notably, to ensure reproducibility it is essential to use homoanhydrides as ammonium enolate precursors with 2-aroyl acrylates, while carboxylic acids can be used with 2-N-tosyliminoacrylates, delivering a range of 3,5,6-substituted dihydropyranones and dihydropyridinones with high enantioselectivity (typically >90 % ee). The derivatization of the heterocyclic core of a 3,5,6-substituted dihydropyranone through hydrogenation is also reported.
- Stark, Daniel G.,Morrill, Louis C.,Cordes, David B.,Slawin, Alexandra M. Z.,O'Riordan, Timothy J. C.,Smith, Andrew D.
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supporting information
p. 395 - 400
(2016/05/19)
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- Facile and direct synthesis of symmetrical acid anhydrides using a newly prepared powerful and efficient mixed reagent
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An efficient mixed reagent for direct synthesis of symmetrical carboxylic anhydrides from carboxylic acids has been prepared. Carboxylic acids are converted to anhydrides using triphenylphosphine/ trichloroisocyanuric acid under mild reaction conditions at room temperature. Short reaction time, excellent yields of products, low cost, availability of reagents, simple experimental procedure, and easy work-up of the products are the main advantages of the presented method.
- Rouhi-Saadabad, Hamed,Akhlaghinia, Batool
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p. 479 - 485
(2015/01/30)
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- Asymmetric Isothiourea-Catalysed Formal [3+2] Cycloadditions of Ammonium Enolates with Oxaziridines
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A highly enantioselective Lewis base-catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis-matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti-stereodefined oxazolidin-4-ones in high d.r., yield and ee. Additionally, the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks.
- Smith, Siobhan R.,Fallan, Charlene,Taylor, James E.,McLennan, Ross,Daniels, David S. B.,Morrill, Louis C.,Slawin, Alexandra M. Z.,Smith, Andrew D.
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supporting information
p. 10530 - 10536
(2015/07/07)
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- Alcohol cross-coupling for the kinetic resolution of diols via oxidative esterification
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We present an organocatalytic C-O-bond cross-coupling strategy to kinetically resolve racemic diols with aromatic and aliphatic alcohols, yielding enantioenriched esters. This one-pot protocol utilizes an oligopeptide multicatalyst, m-CPBA as the oxidant, and N,N-diisopropylcarbodiimide as the activating agent. Racemic acyclic diols as well as trans-cycloalkane-1,2-diols were kinetically resolved, achieving high selectivities and good yields for the products and recovered diols.
- Hofmann, Christine,Schümann, Jan M.,Schreiner, Peter R.
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p. 1972 - 1978
(2015/02/19)
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- 2-Arylacetic anhydrides as ammonium enolate precursors
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Readily prepared 2-arylacetic anhydrides act as convenient ammonium enolate precursors in isothiourea (HBTM-2.1)-mediated catalytic asymmetric intermolecular Michael addition-lactonisation processes, giving diverse synthetic building blocks in good yield
- Morrill, Louis C.,Ledingham, Lyndsay A.,Couturier, Jean-Philippe,Bickel, Jasmine,Harper, Andrew D.,Fallan, Charlene,Smith, Andrew D.
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p. 624 - 636
(2014/01/06)
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- Efficient and convenient synthesis of symmetrical carboxylic anhydrides from carboxylic acids with sulfated zirconia by phase transfer catalysis
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An efficient and convenient procedure for the synthesis of symmetrical carboxylic anhydrides from carboxylic acids with sulfated zirconia by PEG-1000 phase transfer catalysis has been developed. The reactions proceeded under mild and solvent-free conditions to provide the carboxylic anhydrides in good to excellent yields. The product can be isolated by a simple extraction with organic solvent, and the catalyst system can be recycled or reused without any significant loss of catalytic activity.
- Hu, Yu Lin,Zhao, Xing E.,Lu, Ming
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experimental part
p. 255 - 262
(2012/04/17)
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- CASPASE INHIBITORS AND USES THEREOF
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This invention provides novel caspase inhibitors useful for prophylaxis or treatment of a number of pathologies, including, for example, Huntington's disease. In certain embodiments the inhibitors include inhibitors of casepase-3 and/or casepase-6.
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Page/Page column 46
(2010/04/03)
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- Esters of 2-phenylalkanenitriles and antifungal compositions containing them
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Esters of 2-phenylalkanenitriles, such as 3-acetoxy-2-(2-chloro-5-(difluoromethoxy)phenyl)propanenitrile and 3-acetoxy-2-(4-chlorophenyl)propanenitrile, and compositions containing such esters, are useful as fungicides at very low concentrations.
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Page/Page column 7
(2008/12/06)
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- Simple preparation of symmetrical carboxylic acid anhydrides by means of Na2CO3/SOCl2
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A convenient and general method for the synthesis of symmetrical carboxylic acid anhydrides using sodium carbonate/thionyl chloride is described. Copyright Taylor & Francis Group, LLC.
- Kazemi,Kiasat,Mombaini
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p. 3219 - 3223
(2008/02/12)
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- BENZIMIDAZOLE OR INDOLE AMIDES AS INHIBITORS OF PIN1
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The invention relates to compounds of the formula (1) and to pharmaceutically acceptable salts and solvates thereof, wherein the variables are defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula (1) and to pharmaceutical compositions for treating such disorders that contain the compounds of formula (1). The invention also relates to methods of preparing the compounds of formula (1).
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Page/Page column 23
(2010/11/08)
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- Substrate activity screening: A fragment-based method for the rapid identification of nonpeptidic protease inhibitors
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A new fragment-based method for the rapid development of novel and distinct classes of nonpeptidic protease inhibitors, Substrate Activity Screening (SAS), is described. This method consists of three steps: (1) a library of N-acyl aminocoumarins with diverse, low molecular weight N-acyl groups is screened to identify protease substrates using a simple fluorescence-based assay, (2) the identified N-acyl aminocoumarin substrates are optimized by rapid analogue synthesis and evaluation, and (3) the optimized substrates are converted to inhibitors by direct replacement of the aminocoumarin with known mechanism-based pharmacophores. The SAS method was successfully applied to the cysteine protease cathepsin S, which is implicated in autoimmune diseases. Multiple distinct classes of nonpeptidic substrates were identified upon screening an N-acyl aminocoumarin library. Two of the nonpeptidic substrate classes were optimized to substrates with >8000-fold improvements in cleavage efficiency for each class. Select nonpeptidic substrates were then directly converted to low molecular weight, novel aldehyde inhibitors with nanomolar affinity to cathepsin S. This study demonstrates the unique characteristics and merits of this first substrate-based method for the rapid identification and optimization of weak fragments and provides the framework for the development of completely nonpeptidic inhibitors to many different proteases.
- Wood, Warren J. L.,Patterson, Andrew W.,Tsuruoka, Hiroyuki,Jain, Rishi K.,Ellman, Jonathan A.
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p. 15521 - 15527
(2007/10/03)
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- A Cheap, Simple and Efficient Method for the Preparation of Symmetrical Carboxylic Acid Anhydrides
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A manipulatively simple and facile one-pot procedure for the synthesis of symmetrical anhydride is reported. Treatment of carboxylic acids with tosyl chloride in K2CO3 media under solvent free conditions gives the corresponding anhydrides in good to excellent yields in a short reaction time via carboxylic sulfonic anhydride as the key intermediate.
- Kazemi, Foad,Sharghi, Hashem,Nasseri, Mohammad Ali
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p. 205 - 207
(2007/10/03)
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- A convenient method for synthesis of symmetrical acid anhydrides from carboxylic acids with trichloroacetonitrile and triphenylphosphine
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Various carboxylic acids are converted into the corresponding carboxylic acid anhydrides treated with trichloroacetonitrile and triphenylphosphine in the presence of triethylamine at room temperature.
- Kim,Jang
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p. 395 - 399
(2007/10/03)
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- Synthesis and antiplatelet activity of phenyl quinolones
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In our search for novel antiplatelet agents, seven positional phenyl quinolone isomers were synthesized. Preliminary screening confirmed their inhibitory effects against arachidonic acid (AA)-induced platelet aggregation. Varying the substitutional position of the phenyl group had a profound effect on the antiplatelet activity of these isomers. 3-Phenyl-4-quinolone showed the greatest potency and was superior to indomethacin, although the two structures are quite different. The mechanism and pharmacological action of 3-phenyl-4-quinolone are currently under investigation. Copyright (C) 1998 Elsevier Science Ltd.
- Huang, Li-Jiau,Hsieh, Ming-Chieh,Teng, Che-Ming,Lee, Kuo-Hsiung,Kuo, Sheng-Chu
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p. 1657 - 1662
(2007/10/03)
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- A search for quantitative acylation of α-trinositol (1D-myo-inositol 1,2,6-tris(dihydrogen phosphate) pentasodium salt)
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The acylation of α-trinositol is very sensitive to reaction conditions. Competing condensation reactions may give pyrophosphates and cyclic phosphates. Treatment of a tert-ammonium salt corresponding to α-trinositol with carboxylic acid anhydride and DMAP gives a good yield of the expected esters.
- Malmberg, Mats,Rehnberg, Nicola
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p. 459 - 464
(2007/10/03)
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- Diphosphonium fluorosulfonate reagent as a dehydrating agent in organic synthesis
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A facile, one-pot dehydration of organic substrates is afforded by the 'diphosphonium fluorosulfonate' reagent, Ph3P(+)OP(+)Ph3*2SO3F(-).This reagent has been used to convert acids to anhydrides, acid and alcohols to esters, acids and amines to amides and in double dehydrations to form heterocycles.
- Niyogi, Debyani G.,Singh, Sukhjinder,Verma, R. D.
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p. 237 - 238
(2007/10/02)
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- Unusual one-pot formation of a phenylketene trimer ester
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The reaction between phenylacetic acid and acetic anhydride yields in one pot, besides the expected phenylacetic anhydride, the phenyl acetate of pyronone-type phenylketene trimer (7).Characterisation of 7 and a possible mechanism of its formation have been discussed.
- Chakrabarty, M.,Pakrashi, S. C.
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p. 285 - 286
(2007/10/02)
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- Reactions of Carboxylic Acids with "Phosphonium Anhydrides"
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General considerations are outlined for a reagent to extract oxygen from organic molecules by an equivalent of dehydration.Reagents, (R3P+)2O, 2OTf-, were created for the purpose and subjected to a preliminary study.They were found to convert carboxylic acids readily and rapidly to anhydrides, esters, amides, amidines, benzimidazoles, and cyclic aryl ketones in good yields.
- Hendrickson, James B.,Hussoin, Md. Sajjat
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p. 1144 - 1149
(2007/10/02)
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- A CONVENIENT PREPARATION OF CARBOXYLIC ACID ANHYDRIDES USING A "SUPPORTED" PHOSPHORUS PENTOXIDE REAGENT
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Treatment of carboxylic acids with a "supported" phosphorus pentoxide reagent provides a convenient route to the corresponding anhydrides.
- Burton, Stephanie G.,Kaye, Perry T.
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p. 3331 - 3336
(2007/10/02)
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- Fused s-Triazino Heterocycles. XV. 13H-4,6,7,13a,13c-Pentaazabenzochrysene, 13H-4,7,13a,13c-Tetraazabenzochrysene, and 7H-3,7,10,10b-Tetraazacycloheptanaphthalene, Three New Ring Systems
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The reaction of N-cyano-N'-(6-amino-2-pyridyl)acetamidine (5a) and homophthalic anhydride followed by ring closure of the 2--5-methyl-1,3,4,6,9b-pentaazaphenalene intermediate (4a) gave 5-methyl-13-oxo-13H-4,6,7,13a,13c-pentaazabenzochrysene (8a).An analogous series starting with 3-N-(6-amino-2-pyridyl)amino-2-cyano-2-butenenitrile (5b) in place of 5a gave in two steps 5-methyl-13-oxo-13H-4,7,13a,13c-tetraazabenzochrysene-6-carbonitrile (8b).Elemental analysis, ir and pmr spectra of 8a, 8b and several new model compounds aided in confirming the structures of 8a and 8b.The synthesis of one of these model compounds for 5b and phenylacetic anhydride led surprisingly to 2-methyl-9-phenyl-7H-3,7,10,10b-tetraazacycloheptanaphthalene (10) in addition to the expected 2-benzyl-4-cyano-5-methyl-1,3,6,9b-tetraazaphenalene (7b).
- Shaw, John T.,Corbett, Wendy L.,Layman, Deanna L.,Cuny, Gregory D.,Kerschner, Judith L.
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p. 1837 - 1840
(2007/10/02)
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- Acyl Trimethylsilyl Polyphosphates as Activated Esters in Acylation Reactions
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The preparation and application of a new class of activated esters, acyl trimethylsilyl polyphosphates, are described.These complexes, prepared by the reaction of trimethylsilyl carboxylates with phosphorus pentoxide, are versatile acylating agents under relatively mild conditions.Sodium or potassium halides and imidazole are very effective catalysts leading to the in situ generation of reactive acyl halides and acyl imidazolides.Amines, amides, alcohols and phenols, p-thiocresol, carboxylic acids and trimethylsilyl carboxylates, and hexamethyldisilazane have been acylated to give high yields of amides, imides, esters, thioesters, anhydrides and nitriles, respectively.
- Rao, C. Someswara,Rambabu, M.,Srinivasan, P. S.
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p. 407 - 411
(2007/10/02)
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