- Enantioselective formal synthesis of tridemethylisovelleral
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A simple and efficient synthetic route to the bicyclic α,β-unsaturated β-keto ester methyl (3aS,7aS)-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indene-5-carboxylate, a versatile intermediate in the synthesis of biologically active unsaturated 1,4-dialdehydes, is described. The synthesis includes a chirality introducing nonenzymatic asymmetric desymmetrization (ADS) reaction of a cyclic meso-anhydride 4 and a modified Hofmann method for preparing exocyclic dienes. The ester was synthesized in a moderate overall yield (19%) from 6 and with an excellent enantioselectivity (>90%).
- R?me, Daniel,Johansson, Martin,Sterner, Olov
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Read Online
- NOVEL HEPATITIS C VIRUS INHIBITORS
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The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
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Page/Page column 35
(2013/07/05)
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- Phosphine ligands in the Palladium-catalysed methoxycarbonylation of ethene: Insights into the catalytic cycle through an HP NMR spectroscopic Study
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Novel cis-1,2-bis(di-tertbutyl-phosphinomethyl) carbocyclic ligands 6-9 have been prepared and the corresponding palladium complexes [Pd(O 3SCH3)(L-L)][O3SCH3] (L-L = diphosphine) 32-35 synthesised and characterised by NMR spectroscopy and Xray diffraction. These diphosphine ligands give very active catalysts for the palladium-catalysed methoxycarbonylation of ethene. The activity varies with the size of the carbocyclic backbone, ligands 7 and 9, containing four- and six-membered ring backbones giving more active systems. The acid used as co-catalyst has a strong influence on the activity, with excess trifluoroacetic acid affording the highest conversion, whereas excess methyl sulfonic acid inhibits the catalytic system. An in oper-ando NMR spectroscopic mechanistic study has established the catalytic cycle and resting state of the catalyst under operating reaction conditions. Although the catalysis follows the hydride pathway, the resting state is shown to be the hydride precursor complex [Pd(O3SCH3)(L-L)][O3SCH3], which demonstrates that an isolable/detectable hydride complex is not a prerequisite for this mechanism.
- De La Fuente, Veronica,Waugh, Mark,Eastham, Graham R.,Iggo, Jonathan A.,Castillon, Sergio,Claver, Carmen
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scheme or table
p. 6919 - 6932
(2010/08/07)
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- Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor
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A highly potent and selective DGAT-1 inhibitor was identified and used in rodent models of obesity and postprandial chylomicron excursion to validate DGAT-1 inhibition as a novel approach for the treatment of metabolic diseases. Specifically, compound 4a conferred weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1-/- mice.
- Zhao, Gang,Souers, Andrew J.,Voorbach, Martin,Falls, H. Doug,Droz, Brian,Brodjian, Sevan,Yau, Yi Lau,Iyengar, Rajesh R.,Gao, Ju,Judd, Andrew S.,Wagaw, Seble H.,Ravn, Matthew M.,Engstrom, Kenneth M.,Lynch, John K.,Mulhern, Mathew M.,Freeman, Jennifer,Dayton, Brian D.,Wang, Xiaojun,Grihalde, Nelson,Fry, Dennis,Beno, David W. A.,Marsh, Kennan C.,Su,Diaz, Gilbert J.,Collins, Christine A.,Sham, Hing,Reilly, Regina M.,Brune, Michael E.,Kym, Philip R.
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p. 380 - 383
(2008/09/17)
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- INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE TYPE 1 ENZYME
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The present invention relates to compounds of formula (I) wherein R1, R3, X, Q, Z, A, D, m, and n are defined herein. Pharmaceutical compositions and methods for treating DGAT-1 related diseases or conditions are also disclosed.
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Page/Page column 54
(2010/11/29)
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- (Lig)Ni(0) induced preparation of mono- and dicarboxylic acids from cyclopentene and carbon dioxide
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Cyclopentene is shown to be an ideal substrate for coupling reactions with (Lig)nickel(0) systems. By variation of the ligands and addition of promoters, it is possible by successive application of carbon dioxide or carbon monoxide to prepare highly selectively series of cyclopentane- and cyclopentenecarboxylic acids (six examples), 4, 5, 6, 11, 14, 15, cyclopentanedicarboxylic acids (three examples), 7, 8, 12, or 2-hydroxycyclopentanecarboxylic acid (9) in good yields. The C5-skeleton is retained in the products.
- Hoberg,Ballesteros,Sigan,Jegat,Milchereit
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p. 395 - 398
(2007/10/02)
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- Reactivity Patterns in the Rhodium Carbenoid Induced Tandem Cyclization-Cycloaddition Reaction
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The rhodium(II) acetate catalyzed behavior of ο--α-diazoacetophenone was studied.The results obtained are consistent with a mechanism in which the key step involves intramolecular cyclization of the ketocarbenoid onto the oxygen atom of the side chain to give an oxonium ylide intermediate which undergoes either C-H insertion or a competitive 2,3-sigmatropic rearrangement.The reaction of 1-diazo-9-decene-2,5-dione with rhodium(II) acetate results in cyclization of the intermediate rhodium carbenoid to give a six-ring carbonyl ylide which readily undergoes intramolecular dipolar cycloaddition.This reaction does not occur when the keto group of the diazo compound has been replaced by an ester functionality.Similar results were also obtained with cis-2-benzoyl-1-(diazoacetyl)cyclopentane.
- Padwa, Albert,Hornbuckle, Susan F.,Fryxell, Glen E.,Stull, Paul D.
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p. 817 - 824
(2007/10/02)
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- A Study of Stereoselective Hydrolysis of Symmetrical Diesters with Pig Liver Esterase
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Pig liver esterase (PLE) catalyzed hydrolysis of dimethyl esters of symmetrical dicarboxylic acids, including meso-diacids, cis-1,2-cycloalkanedicarboxylic acids, and diacids with a prochiral center, was studied with 14 substrates.The products of these stereoselective hydrolyses are chiral monoesters of dicarboxylic acids, with an enantiomeric excess (e.e.) from 10percent to 100percent.Some of these optically active monoesters are valuable synthons in natural products synthesis.An additivity pattern of α- and β-substituents with the glutaric esters on the stereoselectivity of enzymatic hydrolysis was observed.Analysis of the experimental results leads to a model of enzyme stereoselectivity of diester hydrolysis in which the substitution pattern at α- and β-C-atoms is found to determine the absolute configuration of the resulting monoester.
- Mohr, Peter,Waespe-Sarcevic, Nada,Tamm, Christoph,Gawronska, Krystyna,Gawronsky, Jacek K.
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p. 2501 - 2511
(2007/10/02)
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- Thioalkanoylalkanoic acid compounds
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Thioalkanoylalkanoic acid compounds and salts thereof having the formula STR1 wherein R 1, R 2, R 3 and R 4 each is hydrogen or lower alkyl;R 5 is hydrogen, lower alkanoyl, benzoyl or STR2 A and B each is hydrogen or join together as a polymethylene chain --(CH 2) n -- to complete a 4-, 5- or 6- membered cycloalkyl group, and m is 0 or 1,are angiotensin converting enzyme inhibitors and are useful as hypotensive agents.
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- A ONE STEP SYNTHESIS OF 2,4-DIALKOXYBICYCLOOCTAN-8-ONES. STEREOCHEMICAL ASSIGNEMENTS USING THE LANTHANIDE NMR SHIFT REAGENT,Eu(FOD)3
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Several 2,4-dialkoxybicyclooctan-8-ones have been prepared as mixtures of stereoisomers which could be separated and characterised by 60 MHz 1H NMR spectroscopy using Eu(FOD)3
- Camps, P.,Jaime, C.
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p. 393 - 396
(2007/10/02)
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