- Ni-Catalyzed enantioselective reductive arylcyanation/cyclization of: N -(2-iodo-aryl) acrylamide
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A Ni/(S,S)-BDPP-catalyzed intramolecular Heck cyclization of N-(2-iodo-aryl) acrylamide with 2-methyl-2-phenylmalononitrile was developed to give oxindoles with good enantioselectivities. We found that utilizing such an electrophilic cyanation reagent cou
- Dong, Kaiwu,Ren, Xinyi,Shen, Chaoren,Wang, Guangzhu
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p. 1135 - 1138
(2022/02/03)
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- Synthesis of Cyclopentenones through Rhodium-Catalyzed C-H Annulation of Acrylic Acids with Formaldehyde and Malonates
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An efficient rhodium-catalyzed protocol for the synthesis of cyclopentenones based on a three-component reaction of acrylic acids, formaldehyde, and malonates via vinylic C-H activation is reported. Exploratory studies showed that 5-alkylation of as-prepared cyclopentenones could be realized smoothly by the treatment of a variety of alkyl halides with a Na2CO3/MeOH solution. Excess formaldehyde and malonate led to a multicomponent reaction that afforded the multisubstituted cyclopentenones through a Michael addition.
- Yu, Shuling,Hong, Chao,Liu, Zhanxiang,Zhang, Yuhong
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supporting information
p. 5054 - 5059
(2021/07/20)
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- INHIBITORS OF CYCLIN-DEPENDENT KINASES
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Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
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Paragraph 00433-00434
(2020/01/24)
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- Rh-Catalyzed asymmetric hydroaminomethylation of α-Substituted acrylamides: Application in the synthesis of RWAY
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The successful rhodium-catalyzed asymmetric hydroformylation and hydroaminomethylation of α-substituted acrylamides is described using 1,3-phosphite-phosphoramidite ligands based on a sugar backbone. A broad scope of chiral aldehydes and amines were afforded in high yields and excellent enantioselectivities (up to 99%). Furthermore, the synthetic potential of this method is demonstrated by the single-step synthesis of the brain imaging molecule RWAY.
- B?rner, Armin,Cunillera, Anton,Diéguez, Montserrat,Godard, Cyril,Lutz, Domke,Margalef, Jessica,Miró, Roger,Pamies, Oscar
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supporting information
p. 9036 - 9040
(2020/11/30)
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- SULFONYL-SUBSTITUTED BICYCLIC COMPOUND WHICH ACTS AS ROR INHIBITOR
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Provided is a sulfonyl-substituted bicyclic compound (A) which acts as a RORγ inhibitor, said compound has good RORγ inhibitory activity and is expected to be used for treating diseases mediated by a RORγ receptor in mammals.
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Paragraph 0325; 0327
(2020/08/16)
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- Macrolactam Synthesis via Ring-Closing Alkene-Alkene Cross-Coupling Reactions
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Reported herein is a practical method for macrolactam synthesis via a Rh(III)-catalyzed ring closing alkene-alkene cross-coupling reaction. The reaction proceeded via a Rh-catalyzed alkenyl sp2 C-H activation process, which allows access to macrocyclic molecules of different ring sizes. Macrolactams containing a conjugated diene framework could be easily prepared in high chemoselectivities and Z,E stereoselectivities.
- Goh, Jeffrey,Loh, Teck-Peng,Maraswami, Manikantha
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supporting information
p. 9724 - 9728
(2020/12/21)
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- INHIBITORS OF CYCLIN-DEPENDENT KINASES
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Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
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Paragraph 00399
(2019/11/19)
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- Domino Carbopalladation/C-H Activation as a Quick Access to Polycyclic Frameworks
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A new type of domino reaction for synthesis of heterocycles fusing the important bioactive cores, such as oxindole, indoline, and isoquinoline, is presented. Upon exposure to the very common palladium catalyst, the conceptually designed N-alkenyl iodobiaryls undergo a sequential carbopalladation/C-H activation to build polycyclic frameworks. These novel unique frameworks may provide structure sources in fragment-based drug discovery.
- Saha, Nemai,Wang, Haiwen,Zhang, Shengyi,Du, Yongliang,Zhu, Daqian,Hu, Yumin,Huang, Peng,Wen, Shijun
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supporting information
p. 712 - 715
(2018/02/09)
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- Deciphering Nature's Intricate Way of N,S-Dimethylating l -Cysteine: Sequential Action of Two Bifunctional Adenylation Domains
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Dimethylation of amino acids consists of an interesting and puzzling series of events that could be achieved, during nonribosomal peptide biosynthesis, either by a single adenylation (A) domain interrupted by a methyltransferase (M) domain or by the sequential action of two of such independent enzymes. Herein, to establish the method by which Nature N,S-dimethylates l-Cys, we studied its formation during thiochondrilline A biosynthesis by evaluating TioS(A3aM3SA3bT3) and TioN(AaMNAb). This study not only led to identification of the exact pathway followed in Nature by these two enzymes for N,S-dimethylation of l-Cys, but also revealed that a single interrupted A domain can N,N-dimethylate amino acids, a novel phenomenon in the nonribosomal peptide field. These findings offer important and useful insights for the development and engineering of novel interrupted A domain enzymes to serve, in the future, as tools for combinatorial biosynthesis.
- Mori, Shogo,Garzan, Atefeh,Tsodikov, Oleg V.,Garneau-Tsodikova, Sylvie
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p. 6087 - 6097
(2017/11/27)
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- Synthesis of Enantiomerically Enriched 2-Hydroxymethylalkanoic Acids by Oxidative Desymmetrisation of Achiral 1,3-Diols Mediated by Acetobacter aceti
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The stereoselective desymmetrisation of achiral 2-alkyl-1,3-diols is performed by oxidation of one of the two enantiotopic primary alcohol moieties by means of Acetobacter aceti MIM 2000/28 to afford the corresponding chiral 2-hydroxymethyl alkanoic acids (up to 94 % ee). The procedure, carried out in aqueous medium under mild conditions of pH, temperature and pressure, contributes to enlarge the portfolio of enzymatic oxidations available to organic chemists for the development of sustainable manufacturing processes.
- Brenna, Elisabetta,Cannavale, Flavia,Crotti, Michele,De Vitis, Valerio,Gatti, Francesco G.,Migliazza, Gaia,Molinari, Francesco,Parmeggiani, Fabio,Romano, Diego,Santangelo, Sara
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p. 3796 - 3803
(2016/12/24)
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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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- Asymmetric Hydrogenation of α-Substituted Acrylic Acids Catalyzed by a Ruthenocenyl Phosphino-oxazoline-Ruthenium Complex
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Asymmetric hydrogenation of various α-substituted acrylic acids was carried out using RuPHOX-Ru as a chiral catalyst under 5 bar H2, affording the corresponding chiral α-substituted propanic acids in up to 99% yield and 99.9% ee. The reaction could be performed on a gram-scale with a relatively low catalyst loading (up to 5000 S/C), and the resulting product (97%, 99.3% ee) can be used as a key intermediate to construct bioactive chiral molecules. The asymmetric protocol was successfully applied to an asymmetric synthesis of dihydroartemisinic acid, a key intermediate required for the industrial synthesis of the antimalarial drug artemisinin.
- Li, Jing,Shen, Jiefeng,Xia, Chao,Wang, Yanzhao,Liu, Delong,Zhang, Wanbin
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supporting information
p. 2122 - 2125
(2016/06/01)
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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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- High-valent palladium-promoted formal Wagner-Meerwein rearrangement
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An oxy-palladation, formal Wagner-Meerwein rearrangement and fluorination cascade has been established for generating fluorinated oxazolidine-2,4-diones and oxazolidin-2-ones. The reaction has a broad substrate scope in which both aryl and alkyl groups can be utilized as efficient migrating groups. Experimental evidence suggests that the reaction is initiated by anti-oxy-palladation of the olefin, followed by oxidative generation of an alkyl PdIV intermediate and a concerted migration-fluorination.
- Wu, Hongmiao,Yang, Bin,Zhu, Lin,Lu, Ronghua,Li, Guigen,Lu, Hongjian
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supporting information
p. 5804 - 5807
(2016/11/29)
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- Bifunctional Iminophosphorane Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α-Substituted Acrylate Esters
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The highly enantioselective sulfa-Michael addition of alkyl thiols to unactivated α-substituted acrylate esters catalyzed by a bifunctional iminophosphorane organocatalyst under mild conditions is described. The strong Br?nsted basicity of the iminophosphorane moiety of the catalyst provides the necessary activation of the alkyl thiol pro-nucleophile, while the two tert-leucine residues flanking a central thiourea hydrogen-bond donor facilitate high enantiofacial selectivity in the protonation of the transient enolate intermediate. The reaction is broad in scope with respect to the alkyl thiol, the ester moiety, and the α-substituent of the α,β-unsaturated ester, affords sulfa-Michael adducts in excellent yields (up to >99%) and enantioselectivities (up to 96% ee), and is amenable to decagram scale-up using catalyst loadings as low as 0.05 mol %.
- Farley, Alistair J. M.,Sandford, Christopher,Dixon, Darren J.
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p. 15992 - 15995
(2016/01/15)
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- The synthesis and structure revision of NSC-134754
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The synthesis of emetine analogue NSC-134754, a potent inhibitor of the HIF pathway, has been accomplished and its structure reassigned. The stereochemistry of NSC-134754 has been assigned for the first time using X-ray crystallography and it has been demonstrated that only one diastereoisomer is active against HIF.
- Hickin, Jennie A.,Ahmed, Afshan,Fucke, Katharina,Ashcroft, Margaret,Jones, Keith
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supporting information
p. 1238 - 1240
(2014/01/17)
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- Part II. Development of novel colchicine-derived immunosuppressants with improved pharmacokinetic properties
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We have developed a new series of immunosuppressant with improved pharmacokinetic properties as the second-generation of colchicine analogs, which were designed based on the privileged structure derived from our previous work. In particular, we identified an analog (14), which exhibited a potent in vitro activity (IC50: 5 nM) in MLR and excellent in vivo efficacy in the Zymosan A-induced arthritis model, in the Carrageenan-induced edema model and in the local lymph node assay (LLNA). Analog 14 also revealed a good oral bioavailability (F: 67.3%) in BALB/c mice.
- Chang, Dong-Jo,Lee, Sujin,Jang, Jaebong,Suh, Young-Ger,Kim, Soon-Ok,Kim, Wan-Joo
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p. 6750 - 6755,6
(2012/12/12)
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- POLO-LIKE KINASE INHIBITORS
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Compounds of the following formula are provided for use with kinases: (I) wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates use
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Page/Page column 330-331
(2009/05/29)
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- Asymmetric synthesis of β2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives
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Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4- isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium β-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2′-alkylacryloyl)-4-isopropyl-5,5- dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of β-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of β-amino- β′-hydroxy N-acyl oxazolidinones. The Royal Society of Chemistry.
- Beddow, James E.,Davies, Stephen G.,Ling, Kenneth B.,Roberts, Paul M.,Russell, Angela J.,Smith, Andrew D.,Thomson, James E.
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p. 2812 - 2825
(2008/03/12)
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- Synthesis and evaluation of α,α -disubstituted-3-mercaptopropanoic acids as inhibitors for carboxypeptidase A and implications with respect to enzyme inhibitor design
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2-Ethyl-2-methyl-3-mercaptopropanoic acid (6) and 2-benzyl-2-methyl-3-mercaptopropanoic acid (7) were synthesized and evaluated as inhibitors for carboxypeptidase A (CPA), a prototypical zinc protease with the expectation that the binding affinities of these inhibitors would be augmented over those of 2-ethyl-3-methylsuccinic acid (2) and 2-benzyl-3-methylsuccinic acid (3), respectively, in light of the fact that the sulfhydryl group is a better zinc coordinating moiety than the carboxylate group. Contrary to the expectation, however, the inhibitory potency of 6 was not improved and that of 7 was rather attenuated by the replacement. A probable explanation for the unexpected results is offered.
- Lee, Hyun Soo,Kim, Dong H.
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p. 4685 - 4691
(2007/10/03)
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- Enantioselective hydrogenation of α,β-unsaturated acids. Substrate-modifier interaction over cinchonidine modified Pd/Al2O3
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X-Ray diffraction, IR measurements and catalytic hydrogenation of various substituted acrylic acids in apolar solvents, as well as molecular modelling provide new insight into the nature of the cinchonidine-substrate interaction and a general rule to predict the major enantiomer.
- Borszeky,Mallat,Baiker
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p. 3745 - 3753
(2007/10/03)
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- 3-aryl-2-isoxazolines as antiinflammatory agents
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This invention relates to 3-aryl-2-isoxazoline compounds which are selective inhibitors of phosphodiesterase type IV (PDEIV). The 3-aryl-2-isoxazolines are useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulm
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- Kinetics and Mechanism of Oxidative Alkoxylation of Unsaturated Aldehydes
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Kinetic trends and mechanism of catalytic oxidation of unsaturated aldehydes with hydrogen peroxide in alcohols was studied. The participation of semiacetals of unsaturated aldehydes in the formation of reaction products is established and the dependence
- Kuptsevich,Pikh
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p. 781 - 783
(2007/10/03)
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- OXIDATION OF UNSATURATED ALDEHYDES BY PEROXY ACIDS
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The full composition of the products and the kinetics of their accumulation was studied during the oxidation of a series of unsaturated aldehydes by peroxy acids.The effects of the temperature, the structure of the aldehyde, and the solvent on the reaction rate and quantitative composition of the products were determined.A kinetic model of the reaction is proposed, and its parameters are calculated.New data are obtained on the mechanism of the Baeyer-Villiger reaction as applied to the oxidation of unsaturated aldehydes by peroxy acids.
- Pikh, Z. G.,Samarik, V. Ya.
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p. 1294 - 1306
(2007/10/02)
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- Aminobenzoic and aminocyclohexanecarboylic acid compounds, compositions, and their method of use
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Compounds of the formula inhibit the action of neutral endopeptidase. As a result, such compounds produce diuresis, natriuresis, and lower blood pressure as well as being useful in the treatment of congestive heart failure, relieving pain, and diarrhea when administered to a mammalian host.
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- Electrosynthesis of symmetrical ketones from organic halides and carbon dioxide catalysed by 2,2'-bipyridine-nickel complexes
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The electrochemical reduction of 1 2,2'-bipyridine-nickel complex, in the presence of carbon dioxide in N-methylpyrrolidone or dimethylformamide as solvent gives the corresponding nickel(0) complex associated with two molecules of CO.Oxidative addition of an alkyl halide to this complex, followed by an internal CO shift and reductive elimination, leads to the formation of a symmetrical ketone in high yield along with nickel(II), whereas aryl or vinyl halides mainly give acyl derivatives.The nickel(0) species is electrochemically regenerated, thus giving rise to an efficient catalytic process.The possible mechanism of these reactions is discussed
- Garnier, L.,Rollin, Y.,Perichon, J.
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p. 347 - 358
(2007/10/02)
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- Straightforward Synthesis of 2-Alkenoic Acids from the Corresponding Saturated Aldehydes
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2-Alkenoic acids may be prepared in good yields from saturated aldehydes via α-selenenylation with 4-(phenylseleno)morpholine formed in situ, followed by hydrogen peroxide oxidation.The actual oxidizing agent is benzeneperseleninic acid which is formed in the reaction medium.
- Outurquin, Francis,Paulmier, Claude
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p. 690 - 691
(2007/10/02)
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- Phosphite-Mediated in Situ Carboxyvinylation: A New General Acrylic Acid Synthesis
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Sequential treatment of a 2-halo carboxylic acid with a dialkyl phosphite and an aldehyde or ketone in the presence of 3 equiv of sodium hydride in glyme constitutes a new general acrylic acid synthesis superior to conventional methods.An alkoxide-in-alcohol variant may be used with bromo- or chloroacetic acid and aryl aldehydes to produce cinnamic acids conveniently.The scope and other features of the synthesis are discussed.
- Brittelli, David R.
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p. 2514 - 2520
(2007/10/02)
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