- Cleavage of Carboxylic Esters by Aluminum and Iodine
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A one-pot procedure for deprotecting carboxylic esters under nonhydrolytic conditions is described. Typical alkyl carboxylates are readily deblocked to the carboxylic acids by the action of aluminum powder and iodine in anhydrous acetonitrile. Cleavage of lactones affords the corresponding ω-iodoalkylcarboxylic acids. Aryl acetylates undergo deacetylation with the participation of the neighboring group. This method enables the selective cleavage of alkyl carboxylic esters in the presence of aryl esters.
- Sang, Dayong,Yue, Huaxin,Fu, Yang,Tian, Juan
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p. 4254 - 4261
(2021/03/09)
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- Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)
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The use of mono-substituted malonic acid half oxyesters (SMAHOs) has been hampered by the sporadic references describing their preparation. An evaluation of different approaches has been achieved, allowing to define the best strategies to introduce diversity on both the malonic position and the ester function. A classical alkylation step of a malonate by an alkyl halide followed by a monosaponification gave access to reagents bearing different substituents at the malonic position, including functionalized derivatives. On the other hand, the development of a monoesterification step of a substituted malonic acid derivative proved to be the best entry for diversity at the ester function, rather than the use of an intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials.
- Condon, Sylvie,Le Gall, Erwan,Pichon, Christophe,Presset, Marc,Xavier, Tania
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supporting information
p. 2085 - 2094
(2021/09/02)
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- Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors
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Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.
- Schade, Markus,Merla, Beatrix,Lesch, Bernhard,Wagener, Markus,Timmermanns, Simone,Pletinckx, Katrien,Hertrampf, Torsten
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supporting information
p. 11801 - 11808
(2020/11/26)
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- Exploration of New Biomass-Derived Solvents: Application to Carboxylation Reactions
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A range of hitherto unexplored biomass-derived chemicals have been evaluated as new sustainable solvents for a large variety of CO2-based carboxylation reactions. Known biomass-derived solvents (biosolvents) are also included in the study and the results are compared with commonly used solvents for the reactions. Biosolvents can be efficiently applied in a variety of carboxylation reactions, such as Cu-catalyzed carboxylation of organoboranes and organoboronates, metal-catalyzed hydrocarboxylation, borocarboxylation, and other related reactions. For many of these reactions, the use of biosolvents provides comparable or better yields than the commonly used solvents. The best biosolvents identified are the so far unexplored candidates isosorbide dimethyl ether, acetaldehyde diethyl acetal, rose oxide, and eucalyptol, alongside the known biosolvent 2-methyltetrahydrofuran. This strategy was used for the synthesis of the commercial drugs Fenoprofen and Flurbiprofen.
- Gevorgyan, Ashot,Hopmann, Kathrin H.,Bayer, Annette
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p. 2080 - 2088
(2020/02/20)
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- Exploring the Promiscuous Enzymatic Activation of Unnatural Polyketide Extender Units in Vitro and in Vivo for Monensin Biosynthesis
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The incorporation of new-to-nature extender units into polyketide synthesis is an important source for diversity yet is restricted by limited availability of suitably activated building blocks in vivo. We here describe a straightforward workflow for the biogenic activation of commercially available new-to-nature extender units. Firstly, the substrate scope of a highly flexible malonyl co-enzyme A synthetase from Streptomyces cinnamonensis was characterized. The results were matched by in vivo experiments in which the said extender units were accepted by both the polyketide synthase and the accessory enzymes of the monensin biosynthetic pathway. The experiments gave rise to a series of predictable monensin derivatives by the exploitation of the innate substrate promiscuity of an acyltransferase and downstream enzyme functions.
- Grote, Marius,Schulz, Frank
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p. 1183 - 1189
(2019/03/11)
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- Synthesis and insecticidal activity of mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety
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Mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety were designed, synthesized, and evaluated for their insecticidal activity. Some of the title compounds showed remarkable insecticidal properties against Aphis craccivora. Compound I13 exhibited satisfactory insecticidal activity against A. craccivora. Meanwhile, label-free proteomics analysis of compound I13 treatment identified a total of 821 proteins. Of these, 35 proteins were up-regulated, whereas 108 proteins were down-regulated. Differential expressions of these proteins reflected a change in cellular structure and metabolism.
- Pan, Jianke,Yu, Lu,Liu, Dengyue,Hu, Deyu
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- Design and synthesis of malonamide derivatives as antibiotics against methicillin-resistant staphylococcus aureus
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Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to humans. Most existing antimicrobial drugs, including the β-lactam and quinoxiline classes, are not effective against MRSA. In this study, we synthesized 24 derivatives of malonamide, a new class of antibacterial agents and potentiators of classic antimicrobials. A derivative that increases bacterial killing and biofilm eradication with low cell toxicity was created.
- Su, Jung-Chen,Huang, Yu-Ting,Chen, Chang-Shi,Chiu, Hao-Chieh,Shiau, Chung-Wai
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- Ni-Catalyzed Enantioselective Reductive Diarylation of Activated Alkenes by Domino Cyclization/Cross-Coupling
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A Ni-catalyzed enantioselective reductive diarylation of activated alkenes by domino cyclizative/cross-coupling of two aryl bromides is developed. This reaction proceeds under very mild conditions and shows broad substrate scope, without requiring the use of preformed organometallic reagents. Moreover, this approach provides direct access to various bis-heterocycles bearing all-carbon quaternary centers in synthetically useful yields (up to 81%) with excellent enantioselectivity (>30 examples, 90-99% ee).
- Wang, Kuai,DIng, Zhengtian,Zhou, Zhijun,Kong, Wangqing
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supporting information
p. 12364 - 12368
(2018/10/05)
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- Copper-catalyzed carboxylation of hydroborated disubstituted alkenes and terminal alkynes with cesium fluoride
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A protocol for the hydrocarboxylation of disubstituted alkenes and terminal alkynes providing access to different secondary carboxylic acids and malonic acid derivatives has been developed. This methodology relies on an initial hydroboration using 9-BBN followed by carboxylation with carbon dioxide in the presence of a copper catalyst and the additive, cesium fluoride. Different cyclohexene, styrene, and stilbene derivatives could be utilized, and alkynes could be transformed into their corresponding dicarboxylic acids in good yields. Finally, six different terpenoids were carboxylated using the developed procedure. (Chemical Equation Presented).
- Juhl, Martin,Laursen, Simon L. R.,Huang, Yuxing,Nielsen, Dennis U.,Daasbjerg, Kim,Skrydstrup, Troels
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p. 1392 - 1396
(2017/05/24)
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- Copper-catalyzed intermolecular chloro- and bromotrifluoromethylation of alkenes
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A highly practical copper-catalyzed intermolecular halotrifluoromethylation of alkenes has been developed under mild reaction conditions. A variety of Cl/Br-containing trifluoromethyl derivatives were directly synthesized from a wide range of alkenes, including electron-deficient and unactivated alkenes.
- Fu, Mingyang,Chen, Long,Jiang, Yongpeng,Jiang, Zhong-Xing,Yang, Zhigang
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supporting information
p. 348 - 351
(2016/02/19)
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- Diastereoselective synthesis of trans-3,5-disubstituted dihydrofuran-2(3H)-ones via SmI2-mediated reductive coupling of 2-alkylacrylates of N,N-diisopropyl-2-hydroxybenzamide with aldehydes
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Samarium(II) diiodide has been used to mediate reductive coupling reactions of aldehydes with a variety of substituted acrylates, in both achiral and chiral forms, for accessing substituted dihydrofuran-2(3H)-ones (γ-butyrolactones). Two major issues, concerning with self-dimerization of α-non-branched aliphatic aldehydes and low diastereoselectivity of the products, render limited application of the reductive coupling protocol in total synthesis of natural products. We report here on a novel type of substituted acrylates derived from the 2-amido arenols (HO-Aram) such as N,N-diisopropyl-2-hydroxybenzamide. The acrylates of HO-Aram enable: (a) preferential conjugate reduction of the acrylates than carbonyl reduction of aliphatic aldehydes, leading to diminished aldehyde self-dimerization; and (b) organization of an eight-membered ring among the amide carbonyl oxygen atom and samarium(III) to form a 7/8-bicyclic transition state, resulting in highly diastereoselective protonation of the samarium(III) enolate intermediate. Examples of synthesis of trans-3,5-disubstituted dihydrofuran-2(3H)-ones from 2-alkylacrylates of HO-Aram and aliphatic aldehydes are provided.
- Lai, Yecai,Sun, Lijie,Sit, Man Ki,Wang, Yan,Dai, Wei-Min
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p. 664 - 673
(2016/01/15)
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- POLARIZING PLATE COMPOSITION, POLARIZING PLATE PROTECTIVE FILM, POLARIZER, POLARIZING PLATE, LIQUID CRYSTAL DISPLAY DEVICE, AND COMPOUND USED IN THE LIQUID CRYSTAL DISPLAY DEVICE
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Provided are a polarizing plate composition, a polarizing plate protective film, a polarizer, a polarizing plate, and a liquid crystal display device, which contain a compound represented by the following Formula (I), and a compound. In Formula (I), each of R1 and R2 represents a substituent. X represents an electron-withdrawing group, and Y represents a substituent having a heteroatom or a carbon atom as an atom bonded to a carbon atom substituted with —OR1. Y and X may form a ring by being bonded to each other.
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Paragraph 0433
(2017/01/31)
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- Organocatalytic enantioselective transient enolate protonation in conjugate addition of thioacetic acid to a-substituted n-acryloyloxazolidinones
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Organocatalytic conjugate addition of thioacetic acid to a series of a-substituted N-acryloyloxazolidin-2- ones followed by enantioselective protonation has been studied in the presence of thiourea catalysts derived from cinchona alkaloids. Conjugate addition/protonation adducts have been obtained up to 97% ee and high yields. The methodology could serve as an easy and practical route to the syntheses of useful biologically active molecules.
- Unhale, Rajshekhar A.,Rana, Nirmal K.,Singh, Vinod K.
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supporting information
p. 1911 - 1915
(2013/05/23)
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- Pd(II)-catalyzed intramolecular amidoarylation of alkenes with molecular oxygen as sole oxidant
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Stereoselective palladium-catalyzed synthesis of structurally versatile indoline derivatives, using molecular oxygen as the sole oxidant, is described. New C-N and C-C bonds form across an alkene in an intramolecular manner. The C-N bond-forming step proceeds via a syn-amidopalladation pathway. The moderate kinetic isotope effects (intramolecular KIE = 3.56) suggest that electrophilic aromatic substitution occurs in the arylation step.
- Yip, Kai-Tai,Yang, Dan
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supporting information; experimental part
p. 2134 - 2137
(2011/06/19)
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- Expanding the utility of Bronsted base catalysis: Biomimetic enantioselective decarboxylative reactions
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As a result of the low reactivity of simple esters, the use of them as nucleophiles in direct asymmetric transformations is a long-standing challenge in synthetic organic chemistry. Nature approaches this difficulty through a decarboxylative mechanism, which is used for polyketide synthesis. Inspired by nature, we report guanidine-catalyzed biomimetic decarboxylative C-C and C-N bond-formation reactions. These highly enantioselective decarboxylative Mannich and amination reactions utilized malonic acid half thioesters as simple ester surrogates. It is proposed that nucleophilic addition precedes decarboxylation in the mechanism, which has been investigated in detail through the identification of intermediates by using electrospray ionization (ESI) mass-spectrometric analysis and DFT calculations. Copyright
- Pan, Yuanhang,Kee, Choon Wee,Jiang, Zhiyong,Ma, Ting,Zhao, Yujun,Yang, Yuanyong,Xue, Hansong,Tan, Choon-Hong
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supporting information; experimental part
p. 8363 - 8370
(2011/09/13)
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- Design and synthesis of non-cytotoxic tetrahydrothieno[3,2-c]pyridine derivatives exhibiting complement inhibition activity
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A series of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine derivatives have been synthesized and evaluated for their activity on the activation of human complement (classical pathway) and their intrinsic haemolytic activity. The in vitro assay results of these analogues for inhibition of complement activity reveals improved inhibitory activity for some of the analogues over existing tetrahydrothienopyridine derivatives like Ticlopidine and Clopidogrel. Significantly, these analogues did not exhibit any haemolytic activity and are non-cytotoxic to human cell lines.
- Master, Hoshang E.,Khan, Shabana I.,Poojari, Krishna A.
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- Peptide deformylase inhibitors of Mycobacterium tuberculosis: Synthesis, structural investigations, and biological results
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Bacterial peptide deformylase (PDF) belongs to a subfamily of metalloproteases catalyzing the removal of the N-terminal formyl group from newly synthesized proteins. We report the synthesis and biological activity of highly potent inhibitors of Mycobacterium tuberculosis (Mtb) PDF enzyme as well as the first X-ray crystal structure of Mtb PDF. Structure-activity relationship and crystallographic data clarified the structural requirements for high enzyme potency and cell based potency. Activities against single and multi-drug-resistant Mtb strains are also reported.
- Pichota, Arkadius,Duraiswamy, Jeyaraj,Yin, Zheng,Keller, Thomas H.,Alam, Jenefer,Liung, Sarah,Lee, Gladys,Ding, Mei,Wang, Gang,Chan, Wai Ling,Schreiber, Mark,Ma, Ida,Beer, David,Ngew, Xinyi,Mukherjee, Kakoli,Nanjundappa, Mahesh,Teo, Jeanette W.P.,Thayalan, Pamela,Yap, Amelia,Dick, Thomas,Meng, Wuyi,Xu, Mei,Koehn, James,Pan, Shi-Hao,Clark, Kirk,Xie, Xiaoling,Shoen, Carolyn,Cynamon, Michael
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scheme or table
p. 6568 - 6572
(2009/09/30)
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- A simple method for the alkaline hydrolysis of esters
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A very mild and rapid procedure for the efficient alkaline hydrolysis of esters in non-aqueous conditions has been developed, by the use of dichloromethane/methanol (9:1) as solvent. This method conveniently provides both carboxylic acids and alcohols from the corresponding esters and sodium hydroxide in a few minutes at room temperature. A plausible reaction mechanism is proposed.
- Theodorou, Vassiliki,Skobridis, Konstantinos,Tzakos, Andreas G.,Ragoussis, Valentine
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p. 8230 - 8233
(2008/03/14)
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- Structural studies of racecadotril and its process impurities by NMR and mass spectroscopy
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Three unknown impurities in racecadotril bulk drug at levels below 0.5% were detected by simple reverse phase isocratic high performance liquid chromatography (HPLC). Structures for these impurities were proposed by molecular ion information and their fragmentation pattern obtained by LC-MS and these impurities were confirmed by NMR spectroscopy. The impurities I, II and III were characterized as benzyl 2-methyl carboximido acetate, benzyl 2-phenyl ethyl carboximido acetate, and benzyl 2-(1-benzyl vinyl carboximido) acetate. These structures were further confirmed by co-injecting of synthetic standards of impurities with racecadotril. The mechanism of the formation of these process related impurities is discussed.
- Mallikarjun Reddy,Moses Babu,Sudhakar,Sharma,Sudershan Reddy,Vyas
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p. 994 - 998
(2007/10/03)
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- A new family of low-spin CoIII bis(amidate) complexes with two cis or trans cyanides
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Four low-spin dicyanodicarboxamidocobalt(III) complexes have been prepared from N,N′-bis(8-quinolyl)malonamide derivatives, the malonyl fragment of which was either unsubstituted (Et4N)[Co(BQM)(CN)2] (3a), monosubstituted by a benzyl group (Et4N)[Co(mono-BenzBQM)(CN) 2] (3b), or disubstituted by two benzyl or two phenylethyl groups, (Et4N)[Co(di-BenzBQM)(CN)2] (3c) and (Et 4N)[Co(di-PhEtBQM)(CN)2] (3d), respectively. The X-ray crystal structures of 3a and 3c reveal that the tetradentate ligand adopts a helical or a planar configuration around the cobalt centre of 3a and 3c, respectively. Complexes 3a-3d were characterised in solution by 1H NMR spectroscopy by 1D and 2D COSY H-H techniques. The solid-state structures of 3a and 3c are retained in solution, and complexes 3b and 3d adopt structures similar to 3a and 3c, respectively, showing that the level of the malonic substitution determines the configuration of the tetradentate ligand around the cobalt centre and forces the cyanide ligands to adopt either cis or trans orientations. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Rotthaus, Olaf,LeRoy, Sophie,Tomas, Alain,Barkigia, Kathleen M.,Artaud, Isabelle
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p. 1545 - 1551
(2007/10/03)
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- Microwave assisted hydrolysis of Meldrum's acid derivatives and decarboxylation of derived malonic acids
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Microwave induced hydrolysis of alkyl Medrum's acids and decarboxylation of derived malonic acids using poly-4-vinylpyridine as a catalyst gives high yields of carboxylic acids in a short time.
- Helavi,Solabannavar,Desai,Mane
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p. 174 - 175
(2007/10/03)
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- Design and pharmacological activity of phosphinic acid based NAALADase inhibitors
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A novel series of phosphinic acid based inhibitors of the neuropeptidase NAALADase are described in this work. This series of compounds is the most potent series of inhibitors of the enzyme described to date. In addition, we have shown that these compounds are protective in animal models of neurodegeneration. Compound 34 significantly prevented neurodegeneration in a middle cerebral artery occlusion model of cerebral ischemia. In addition, in the chronic constrictive model of neuropathic pain, compound 34 significantly attenuated the hypersensitivity observed with saline-treated animals. These data suggest that NAALADase inhibition may provide a new approach for the treatment of both neurodegenerative disorders and peripheral neuropathies.
- Jackson,Tays,Maclin,Ko,Li,Vitharana,Tsukamoto,Stoermer,Lu,Wozniak,Slusher
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p. 4170 - 4175
(2007/10/03)
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- Process for the synthesis of α-substituted acrylic acids and their application
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Process for the synthesis of a-substituted acrylic acids and their application. Process for the synthesis of a-substituted acrylic acids of general formula (I) and their application to the synthesis of N- (mercaptoacyl) aminoacid derivatives of formula (II). STR1
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- Pd(O)-CATALYZED ELECTROREDUCTIVE CARBOXYLATION OF ARYL HALIDES, β-BROMOSTYRENE, AND ALLYL ACETATES WITH CO2
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Electroreductive carboxylation of aryl halides, β-bromostyrene, and allyl acetates has been performed in an aprotic solvent saturated with carbon dioxide in the presence of a catalytic amount of PdCl2(Ph3P)2 and/or Pd(Ph3P)4.
- Torii, Sigeru,Tanaka, Hideo,Hamatani, Takeshi,Morisaki, Kazuo,Jutand, Anny,et al.
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p. 169 - 172
(2007/10/02)
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