- Synthesis of Vicinal Quaternary All-Carbon Centers via Acid-catalyzed Cycloisomerization of Neopentylic Epoxides
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We report our studies on the development of a catalytic cycloisomerization of 2,2-disubstituted neopentylic epoxides to produce highly substituted tetralins and chromanes. Termination of the sequence occurs via Friedel-Crafts-type alkylation of the remote (hetero)arene linker. The transformation is efficiently promoted by sulfuric acid and proceeds best in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as the solvent. Variation of the substitution pattern provided detailed insights into the migration tendencies and revealed a competing disproportionation pathway of dihydronaphthalenes.
- Schmid, Matthias,Sokol, Kevin R.,Wein, Lukas A.,Torres Venegas, Sofia,Meisenbichler, Christina,Wurst, Klaus,Podewitz, Maren,Magauer, Thomas
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supporting information
p. 6526 - 6531
(2020/09/02)
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- 5-(PYRIDIN-3-YL)OXAZOLE ALLOSTERIC MODULATORS OF M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
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Provided are 5-(pyridin-3-yl) oxazole compounds, the compositions comprising these compounds and the uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.
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Page/Page column 31-32
(2019/01/16)
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- 3-(1H-PYRAZOL-4-YL)PYRIDINE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
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The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.
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Page/Page column 30-31
(2019/01/16)
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- CASPASE INHIBITOR AND PHARMACEUTICAL COMPOSITION, USE AND THERAPEUTIC METHOD THEREOF
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Disclosed are a class of compounds as a caspase inhibitor, and in particular the compound as shown in formula (I) or a pharmaceutically acceptable salt thereof, and the use of the compound in treating caspase-related diseases.
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- 3- (1H-PYRAZOL-4-YL) PYRIDINEALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR
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The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.
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Page/Page column 42
(2017/07/14)
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- Stereospecific Construction of Contiguous Quaternary All-Carbon Centers by Oxidative Ring Contraction
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Oxidative ring contraction of cyclic α-formyl ketones was facilitated by the action of H2O2under operationally simple and environmentally benign reaction conditions. The process was highly regioselective and enables stereospecific construction of contiguous quaternary all-carbon centers from stereodefined all-substituted all-cyclic ketones. The asymmetric syntheses of (+)-cuparene and (+)-tochuinyl acetate were also successively achieved by taking advantage of this novel protocol.
- Yu, Xin,Hu, Jiadong,Shen, Zhigao,Zhang, Hui,Gao, Jin-Ming,Xie, Weiqing
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p. 350 - 353
(2016/12/30)
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- New Strategy for Forging Contiguous Quaternary Carbon Centers via H 2 O 2 -Mediated Ring Contraction
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Stereospecific construction of contiguous quaternary carbon centers constitutes a major challenge in natural product synthesis. A general protocol that enables stereospecific construction of all stereoisomers of such a moiety remains elusive. In this article, we will discuss the oxidative ring contraction of all-substituted cyclic α-formyl ketones mediated by H 2 O 2, which provides a facile access to the stereospecific construction of contiguous quaternary carbon centers.
- Hu, Jiadong,Yu, Xin,Xie, Weiqing
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p. 2517 - 2524
(2017/09/28)
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- Nickel-Catalyzed Addition-Type Alkenylation of Unactivated, Aliphatic C-H Bonds with Alkynes: A Concise Route to Polysubstituted γ-Butyrolactones
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(Chemical Equation Presented). Through the nickel-catalyzed chelation-assisted C-H bond activation strategy, the addition-type alkenylation of unreactive β-C(sp3)-H bonds of aliphatic amides with internal alkynes is developed for the first time to produce γ,δ-unsaturated carboxylic amide derivatives. The resulting alkenylated products can further be transformed into polysubstituted γ-butyrolactones with pyridinium chlorochromate (PCC).
- Li, Mingliang,Yang, Yudong,Zhou, Danni,Wan, Danyang,You, Jingsong
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p. 2546 - 2549
(2015/05/27)
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- Palladium-catalyzed C(sp3)-H activation: A facile method for the synthesis of 3,4-dihydroquinolinone derivatives
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3,4-Dihydroquinolinones were synthesized by the palladium-catalyzed, oxidative-addition-initiated activation and arylation of inert C(sp 3)-H bonds. Pd(OAc)2 and P(o-tol)3 were used as the catalyst and ligand, respectively, to improve the efficiency of the reaction. A further advantage of this reaction is that it could be performed in air. A relatively rare seven-membered palladacycle was proposed as a key intermediate of the catalytic cycle.
- Yan, Jia-Xuan,Li, Hu,Liu, Xiang-Wei,Shi, Jiang-Ling,Wang, Xin,Shi, Zhang-Jie
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supporting information
p. 4945 - 4949
(2014/05/20)
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- β-Arylation of carboxamides via iron-catalyzed C(sp3)-H bond activation
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A 2,2-disubstituted propionamide bearing an 8-aminoquinolinyl group as the amide moiety can be arylated at the β-methyl position with an organozinc reagent in the presence of an organic oxidant, a catalytic amount of an iron salt, and a biphosphine ligand at 50 C. Various features of selectivity and reactivity suggest the formation of an organometallic intermediate via rate-determining C-H bond cleavage rather than a free-radical-type reaction pathway.
- Shang, Rui,Ilies, Laurean,Matsumoto, Arimasa,Nakamura, Eiichi
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p. 6030 - 6032,3
(2013/05/22)
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- The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: A change in direction in the search for a second generation HCV NS3 protease inhibitor
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In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tert-butyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration.
- Bennett, Frank,Huang, Yuhua,Hendrata, Siska,Lovey, Raymond,Bogen, Stephane L.,Pan, Weidong,Guo, Zhuyan,Prongay, Andrew,Chen, Kevin X.,Arasappan, Ashok,Venkatraman, Srikanth,Velazquez, Francisco,Nair, Latha,Sannigrahi, Mousumi,Tong, Xiao,Pichardo, John,Cheng, Kuo-Chi,Girijavallabhan, Viyyoor M.,Saksena, Anil K.,Njoroge, F. George
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scheme or table
p. 2617 - 2621
(2010/07/05)
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- CATHEPSIN S INHIBITORS
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Compounds of the formula (I) where R1 is C1-C4 straight or branched alkyl, optionally substituted with up to three substituents selected from halo and hydroxy; R2 is halo, hydroxy, methyloxy, or C1-C2 alkyl, which alkyl is optionally substituted with up to three halogens or an hydroxy or a methyloxy; D is - C3-C7 alkylene-, thereby defining a cycloalkyl ring; E is -C(=O)-, -S(=O)m-, -NRdS(=O)m-, -NRaC(=O)-, -OC(=O)-, R3 is an optionally substituted carbocyclic or heterocyclic ring R10 is H, ORc, SRc or together with the gem H is =O or (ORc)2; Ra is independently selected from H, C1-C4 alkyl; have utility in the inhibition of cathepsin S and are thus useful pharmaceuticals against disorders such as autoimmune disorders and chronic pain.
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Page/Page column 28-29
(2010/11/08)
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- CATALYTICS ASYMMETRIC ACTIVATION OF UNACTIVATED C-H BONDS, AND COMPOUNDS RELATED THERETO
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One aspect of the present invention is directed in part to catalytic and stereoselective functionalization of unactivated C-H bonds of simple organic substrates. The compounds and methods provided herein allow one to control the stereochemistry in a C-H activation step, activate substrates containing α-hydrogens next to the directing group, and remove a directing group under mild conditions. One aspect of the present invention relates to a transition-metal-catalyzed method for selective and asymmetric oxidation of carbons located in a β- or γ-position relative to an auxiliary. Another aspect of the invention relates to the enantiomerically-enriched substrates and the enantiomerically-enriched products formed via said method. In certain embodiments, oxazoline and oxazinone directing groups are used. In addition, the Boc protecting group has been identified as a directing group which does not necessitate removal.
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Page/Page column 76-77; 89-90
(2010/10/20)
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- Palladium(I) Carbonyl Cation-Catalyzed Carbonylation of Olefins and Alcohols in Concentrated Sulfuric Acid
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A new palladium catalyst was found to exhibit high catalytic activity for carbonylation of olefins and alcohols. cyclo-Bis(μ-carbonyl)dipalladium(I) cation (1) with bridging CO ligands is formed by reductive carbonylation of palladium sulfate, PdSO4, in concentrated H2SO4. When an olefin or alcohol is added, complex 1 changes to a new complex (2) with terminal CO ligands, and tertiary carboxylic acids are obtained in high yields at room temperature and atmospheric pressure of CO. IR and 13C NMR studies suggest that complex 2 may be tentatively formulated to be [Pd2(CO)2]2+, in which the terminal CO ligands are chemically equivalent. Complex 1 is a catalyst precursor, and complex 2 functions as an active species for the carbonylation of olefins and alcohols. The catalytic behavior of the palladium carbonyl catalyst supports the recently proposed reaction mechanism involving an olefin-metal-CO complex as an intermediate for the catalytic carbonylation of olefins and alcohols in strongly acidic solution.
- Xu, Qiang,Souma, Yoshie,Umezawa, Junya,Tanaka, Mutsuo,Nakatani, Hisako
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p. 6306 - 6311
(2007/10/03)
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- Pesticidal compounds
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This invention relates to 1,1,1,4-substituted naphthaline compounds, compositions, processes for their preparation and processes for their use as pesticides, especially insecticides, acaricides and fungicides.
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- A New Gold Catalyst: Formation of Gold(I) Carbonyl, [Au(CO)n]+ (n = 1, 2), in Sulfuric Acid and Its Application to Carbonylation of Olefins
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A new gold catalyst, [Au(CO)n]+ (n = 1, 2), was synthesized by using a facile method from commercial gold(III) oxide, Au2O3, in concentrated H2SO4, which exhibits high catalytic activity for carbonylation of olefins. The gold monocarbonyl [Au(CO)]+ (1) and dicarbonyl [Au(CO)2]+ (2) cations coexist in H2SO4 solution, the former of which is much more stable than the latter. Both of the carbonyls show IR spectra of vCO (2194, 2208 cm-1) higher than that of free CO (2143 cm-1), indicating nonclassical (σ-only) gold-CO bonding. The gold carbonyl complexes coexisting in the concd H2SO4 solution exhibit a single resonance in the 13C NMR spectrum at 171 ppm at ambient temperature and pressure, reflecting rapid CO exchange between 1 (164 ppm) and 2 (175 ppm). The nonclassical gold(I) carbonyl solution worked as an excellent catalyst, with which olefins reacted with CO to give tert-carboxylic acids in good yields at room temperature and atmospheric pressure. The gold(I) dicarbonyl cation 2 was found to function as an active species for the carbonylation. An olefin-gold(I)-carbonyl complex was proposed as a possible intermediate in the metal carbonyl-catalyzed carbonylation in the strongly acidic medium.
- Xu, Qiang,Imamura, Yuki,Fujiwara, Masahiro,Souma, Yoshie
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p. 1594 - 1598
(2007/10/03)
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- ETHOXYCARBONYLATION OF CYCLOHEXANOL BY ETHYL FORMATE UNDER CONDITIONS OF CATALYSIS BY SULFURIC ACID
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The catalytic ethoxycarbonylation of cyclohexanol by ethyl formate in the presence of concentrated sulfuric acid at 25-55 deg C and atmospheric pressure was investigated.The products are cyclohexanecarboxylic and 1-methyl-1-cyclopentanecarboxylic acid and their ethyl esters.A reaction mechanism is proposed.
- Ordyan, M. B.,Stepanyan, A. A.,Pirozhkov, S. D.,Manukyan, Sh. M.,Grigoryan, V. S.,Lapidus, A. L.
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p. 2290 - 2292
(2007/10/02)
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- Preparation of 15-deoxy-16-hydroxyprostaglandins
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Analogues of PGE1 having the structural formula, STR1 in which J is R-hydroxymethylene or S-hydroxymethylene; R1 is hydrogen; R2 is hydrogen or together with R4 is a methylene chain of 2 to 3 carbon atoms such that a cycloalkyl of 5 to 6 carbon atoms inclusive is formed; R3 is hydrogen or methyl, or together with R4 is a methylene or a lower alkylated methylene chain of 2 to 5 carbon atoms such that a cycloalkyl or a lower alkylated cycloalkyl of 4 to 7 carbon atoms inclusive is formed, or together with R4 is bicycloalkyl or bicycloalkenyl moiety having the formula: STR2 SUCH THAT A BICYCLOALKYL OR BICYCLOALKENYL COMPOUND IS FORMED, WHEREIN M AND N ARE INTEGERS HAVING A VALUE FROM 0 TO 3, P IS AN INTEGER HAVING A VALUE FROM 0 TO 4 AND Q IS AN INTEGER HAVING A VALUE OF FROM 1 TO 4 AND WHEREIN THE DOUBLE BOND OF SUCH BICYCLOALKENYL IS IN THE M, N, P, OR Q BRIDGE; R4 is hydrogen or methyl or together with R2 or R3 forms a cycloalkyl or bicycloalkyl or bicycloalkenyl as defined above, or together with R5 is a methylene chain of 3 to 5 carbon atoms such that a cycloalkyl of 4 to 6 carbon atoms inclusive is formed; R5 is selected from the group consisting of hydrogen, straight-chain alkyl having from 1 to 3 carbon atoms or together with R4 forms a cycloalkyl as defined above; and R6 is hydrogen or straight-chain alkyl having from 1 to 3 carbon atoms are disclosed. Pge1 ester analogues of the above formula, limited to the structures wherein two of R2, R3 R4 and R5 form a cycloalkyl, lower alkylated cycloalkyl, bicycloalkyl or bicycloalkenyl are also disclosed. The prostaglandin analogues selectively produce bronchodilation and decrease gastric secretion in vivo. Methods of preparing the analogues and starting materials required in the synthesis of the analogues are also disclosed.
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