- One-Pot Sequential Photoredox Chemistry and Asymmetric Transfer Hydrogenation with a Single Catalyst
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A sequential process is reported, in which different photoredox reactions are placed in sequence with asymmetric transfer hydrogenations of aryl ketones to provide a diverse set of chiral alcohols with enantioselectivities of up to 99 % ee. The method relies on a single chiral-at-metal catalyst which is added at the beginning of the two step sequence and only a final purification of the reaction product is required.
- Zhang, Xiao,Qin, Jie,Huang, Xiaoqiang,Meggers, Eric
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Read Online
- Transition Metal-Free Alkyne-Aldehyde Reductive C?C Coupling trough Cascade Borylation/Olefin Isomerization
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A direct approach to γ-keto esters through cascade alkyne-aldehyde reductive C?C coupling of propargyl esters and aromatic aldehydes under transition-metal-free (TM-free) fashion was developed. Compared with multistep processes, this procedure provides a
- Khan, Imran,Luo, Zhibin,Xu, Yin,Xie, Jimin,Zhu, Weihua,Liu, Bin
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- Biocatalytic Asymmetric Reduction of γ-Keto Esters to Access Optically Active γ-Aryl-γ-butyrolactones
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An efficient stereoselective syntheses of a series of functionalized optically active γ-aryl-γ-butyrolactones is achieved by enzymatic asymmetric reduction of the corresponding sterically demanding γ-keto esters employing wild-type and recombinant alcohol dehydrogenases. The best stereoselectivities for the reduction via hydrogen transfer was obtained with two short chain dehydrogenases (SDRs) of complementary stereospecificity from Aromatoleum aromaticum, namely the Prelog-specific NADH-dependent (S)-1-phenylethanol dehydrogenase [(S)-PED] and the anti-Prelog-specific (R)-1-(4-hydroxyphenyl)-ethanol dehydrogenase [(R)-HPED], respectively.Biotransformations catalyzed by both enzymes, followed by TFA-catalyzed cyclization of the resulting γ-hydroxy esters, furnished the respective (S)- and (R)-configured products with exquisite optical purity (up to >99% ee). The synthetic value was demonstrated on preparative scale for the asymmetric bioreduction of the model compound, methyl 4-oxo-4-phenylbutanoate, affording optically pure (S)-γ-phenyl-γ-butyrolactone (>99% ee) in 67–74% isolated yield at 89–95% conversion depending on the applied scale. (Figure presented.).
- ??d?o-Dobrowolska, Anna,Borowiecki, Pawe?,Heider, Johann,Kroutil, Wolfgang,Reiter, Tamara,Schühle, Karola,Szaleniec, Maciej,Tataruch, Mateusz,Telatycka, Natalia
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- Bcl-2 INHIBITORS
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Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases including cancers and treating autoimmune disease, and a pharmaceutical composition comprising the same.
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- TBAI/TBHP-Promoted Generation of Malonyl Radicals: Oxidative Coupling with Styrenes Leads to γ-Keto Diesters
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A metal-free protocol for oxidative coupling of malonic esters with styrenes to form γ-keto diesters has been developed. Key to the success of this process is the generation of malonyl radicals from unfunctionalized malonic esters under organo-catalysis conditions with TBAI and TBHP. This process tolerates both terminal and internal olefins with diverse malonic esters. It provides a new green metal-free alternative to traditional metal mediated process for generation of malonyl radicals and there by γ-keto diesters.
- Chowdhury, Soumyadeep Roy,Hoque, Injamam Ul,Maity, Soumitra
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p. 2824 - 2828
(2018/09/20)
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- Organoselenium-catalyzed synthesis of oxygen- and nitrogen-containing heterocycles
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A new and efficient approach for the synthesis of oxygen and nitrogen heterocycles by organoselenium catalysis has been developed. The exo-cyclization proceeded smoothly under mild conditions with good functional group tolerance and excellent regioselectivity. Mechanistic studies revealed that 1-fluoropyridinium triflate is key for oxidative cyclization.
- Guo, Ruizhi,Huang, Jiachen,Huang, Haiyan,Zhao, Xiaodan
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p. 504 - 507
(2016/02/18)
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- Remote activation of the nucleophilicity of isatin
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The concept of the remote activation of reactivity was first applied in asymmetric organocatalysis. An isatin 3-phenylimine derivative acts as a donor in the thiourea catalyzed asymmetric addition to unsaturated 1,4-ketoesters, affording aza-Michael adducts in high enantiomeric purity and yield.
- Zari, Sergei,Kudrjashova, Marina,Pehk, Tonis,Lopp, Margus,Kanger, Tonis
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p. 1740 - 1743
(2014/04/17)
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- Design and synthesis of tri-substituted chiral pyrrolidin-2-one derivatives as CCR4 antagonists
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A series of tri-substituted chiral pyrrolidin-2-one derivatives have been designed and synthesized as CC chemokine receptor 4 (CCR4) antagonists. The structure of CCR4 was built by homology modeling. Asymmetric synthesis was applied to synthesize the R,R configuration chiral pyrrolidin-2-one scaffold. The stereoisomeric configurations of the compounds were identified by 2D 1H-1H COSY spectroscopy and 1D NOESY spectroscopy. This method was more economical and convenient than traditional X-ray single crystal diffraction. In addition, the interactions between these compounds and the N-terminal extracellular tail of CCR4 were studied using capillary zone electrophoresis. The CCR4 chemotaxis inhibition effect was tested in CCR4-transfected HEK293 cells. Several compounds showed potent activities as CCR4 antagonists. Among these compounds, 1c is the most active one. Its apparent binding constant of CZE experiment result is (1.569±0.11)×10 5 L·mol-1, and its percentage inhibition of the HEK293/CCR4 cells migration with the concentration of 1 μmol·L -1 in DMSO is 59%. And compound 1f has slightly higher affinity to N-terminal of CCR4 according to its apparent binding constant than 1b because of the introduced ester linkage. Further studies on the mechanism of these compounds are in progress. The structure of CCR4 based on bovine rhodopsin was built through homology modeling. And six tri-substituted chiral pyrrolidin-2-one derivatives have been designed and synthesized as CCR4 antagonists. Several of these compounds show high inhibitory effect in cell assays and higher affinity for the N-terminal of CCR4. Among the compounds, 1c exhibited excellent activity. Copyright
- Sun, Wei,Tian, Linjie,Qi, Hui,Jiang, Dan,Wang, Ying,Li, Song,Xiao, Junhai,Yang, Xiaohong
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p. 1144 - 1152
(2013/10/21)
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- Cross metathesis of allyl alcohols: How to suppress and how to promote double bond isomerization
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Under standard conditions the cross metathesis of allyl alcohols and methyl acrylate is accompanied by the formation of ketones, resulting from uncontrolled and undesired double bond isomerization. By conducting the CM in the presence of phenol, the catalyst loading and the reaction time required for quantiative conversion can be reduced, and isomerization can be suppressed. On the other hand, consecutive isomerization can be deliberately promoted by evaporating excess methyl acrylate after completing cross metathesis and by adding a base or silane as chemical triggers.
- Schmidt, Bernd,Hauke, Sylvia
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p. 4194 - 4206
(2013/07/05)
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- NAPHTHALENE DERIVATIVE
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The present invention provides compounds which can regulate VCP activity. The present invention provides the compound of formula (I) (R is as defined in the description) or oxides, esters, prodrugs, pharmaceutically acceptable salts or solvates thereof. The compounds can regulate VCP activity, and thus are useful for treating VCP-mediated diseases such as neurodegenerative diseases.
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Paragraph 0311
(2013/06/27)
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- AGENT FOR TREATMENT OF EYE DISEASES
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The present invention provides agents effective to treat eye diseases, pharmaceutical compositions comprising them, methods for preparing pharmaceuticals for treatment of eye diseases comprising using the agents, use of the agents in manufacture of pharma
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Paragraph 0175-0176
(2013/08/15)
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- Asymmetric synthesis of di- and trisubstituted cyclopropanes through an intramolecular ring closure
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An asymmetric synthesis of di- and trisubstituted cyclopropanes proceeding through an intramolecular ring closure of activated chiral benzyl alcohols has been developed. The chiral alcohol intermediates are obtained from asymmetric reduction of readily av
- Kallemeyn, Jeffrey M.,Mulhern, Mathew M.,Ku, Yi-Yin
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supporting information; experimental part
p. 535 - 538
(2011/05/04)
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- One-pot synthesis of oxo acid derivatives by RhI-catalyzed chelation-assisted hydroacylation
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Various oxo acid derivatives were obtained directly from the reaction of aliphatic and aromatic aldehydes with ω-alkenoic acid derivatives in the presence of rhodium(I) complexes and 2-amino-3-picoline. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Jo, Eun-Ae,Jun, Chul-Ho
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p. 2504 - 2507
(2007/10/03)
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- Spiro-hydantoin compounds useful as anti-inflammatory agents
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Compounds having the formula (I), and pharmaceutically-acceptable salts, hydrates, enantiomers, and diastereomers, and prodrugs thereof, are useful as inhibitors of LFA-1/ICAM and as anti-inflammatory agents, wherein L and K are O or S; Z is N or CR4b; Ar is an optionally-substituted aryl or heteroaryl; G is a linker attached to T or M or is absent; J, M and T are selected to define a three to six membered saturated or partially unsaturated non-aromatic ring; and R2 R4a, R4b, and R4c are as defined in the specification.
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Page/Page column 35
(2008/06/13)
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- Facile oxidation of aldehydes to acids and esters with Oxone
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(Matrix presented) A highly efficient, mild, and simple protocol is presented for the oxidation of aldehydes to carboxylic acids utilizing Oxone as the sole oxidant. Direct conversion of aldehydes in alcoholic solvents to their corresponding ester products is also reported. These reactions may prove to be valuable alternatives to traditional metal-mediated oxidations.
- Travis, Benjamin R.,Sivakumar, Meenakshi,Hollist, G. Olatunji,Borhan, Babak
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p. 1031 - 1034
(2007/10/03)
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- Heteroaryl butyric acids and their derivatives as inhibitors of matrix metalloproteinases
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Heteroaryl butyric acid compounds and derivatives are described as well as methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A, collagenase-3, and stro
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- Biphenyl butyric acids and their derivatives as inhibitors of matrix metalloproteinases
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Biphenyl butyric acid compounds and derivatives are described as well as acid methods for the preparation and pharmaceutical compositions of same, which are useful as inhibitors of matrix metalloproteinases, particularly gelatinase A (72 kD gelatinase) an
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- Intermolecular hydroacylation of acrylate esters: A new route to 1,4-dicarbonyls
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1,4-Dicarbonyl compounds can be prepared using a Rh(I) mediated hydroacylation reaction between (2-aminopicolyl)imines and acrylate esters followed by acid hydrolysis.
- Willis,Sapmaz
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p. 2558 - 2559
(2007/10/03)
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- Pd-catalyzed inter- and intramolecular carbene transfer from group 6 metal-carbene complexes
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The use of group 6 metal-carbene complexes in inter- and intramolecular carbene transfer reactions has been studied. Thus, pentacarbonyl[(aryl)(methoxy)carbene]chromium(0) and tungsten complexes, 10, efficiently dimerize at room temperature in the presenc
- Sierra,Del Amo,Mancheno,Gomez-Gallego
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p. 851 - 861
(2007/10/03)
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- THERAPEUTIC AGENT FOR DIABETES
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A therapeutic agent for diabetes, which comprises a compound of the formula [I] wherein Xis a group of the formula wherein R4and R5are the same or different and each is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, and R6is a hydrogen atom or an amino-protecting group; R1is an optionally substituted alkyl having 1 to 5 carbon atoms, an optionally substituted alkenyl having 2 to 6 carbon atoms and the like, R2is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, R2' is a hydrogen atom, and R3is an optionally substituted alkyl having 1 to 5 carbon atoms and the like, a prodrug thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof and a solvate thereof. The compound of the present invention shows superior blood sugar decreasing action on the state of hyperglycemia, but does not affect the blood sugar when it is in the normal range or in the hypoglycemic state, which means that it is free of serious side effects such as hypoglycemia. Therefore, the compound of the present invention is useful as a therapeutic drug for diabetes and also useful as a preventive of the chronic complications of diabetes.
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- Isoindol-1-one analogues of 4-(2'-methoxyphenyl)-1-[2'-[N-(2'-pyridyl)- p-iodobenzamido]ethyl]piperazine (p-MPPI) as 5-HT1(A) receptor ligands
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In developing radioiodinated antagonists for in vivo imaging of 5- HT(1A) receptors with SPECT, a series of new arylpiperazine benzamido derivatives, including 4-(2'-methoxyphenyl)-l-[2'-[N-(2-pyridyl)-p- iodobenzamido]ethyl]piperazine (p-MPPI, 31) (K(d) = 0.36 nM), as potential ligands for 5-HT1(A) receptors were reported previously. However, rapid in vivo metabolism may have caused the breakdown of the amide bond of [123I]- 31 and rendered this agent obsolete as an in vivo imaging agent in humans. To improve the in vivo stability of 31, a series of cyclized amide analogues were designed and synthesized. In vitro binding, metabolic stability, and in vivo biodistribution of these new derivatives were investigated. Several five-membered-ring isoindol-1-ones displayed very high in vitro binding affinity, especially 2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-6- nitro-3-phenyl-2,3-dihydroisoindol-1-one, 15, 3-hydroxy-6-iodo-2-{2-[4-(2- methoxyphenyl)piperazin-1-yl]ethyl}-3-phenyl-2,3-dihydroisoindol-1-one, 18, and 6-iodo-2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl)}-3-phenyl-2,3- dihydroisoindol-1-one, 21, which showed K(i) values of 0.05, 0.65, and 0.07 nM, respectively. The affinities for 5-HT1(A) receptors of other cyclized amide derivatives, 5-(4-bromophenyl)-1-{2-[4-(2-methoxyphenyl)piperazin-1- yl]ethyl}pyrrolidin-2-one, 25, 5-(4-iodophenyl)-1,{2-[4-(2- methoxyphenyl)piperazin-1-yl]ethyl}pyrrolidin-2-one, 27, and 2-{2-[4-(2- methoxyphenyl)piperazin-1-yl]ethyl}-2,3-dihydroisoindol-1-one, 29, were 1.09, 2.54, and 14.9 nM, respectively. Compared to [125I]-31, iodinated cyclized amide derivatives [125I]-21 and [125I]-27 displayed a slower metabolism in human liver microsomal and cytosolic preparations. Biodistribution of [125I]-21 and [125I]-27 in rats (after an iv injection) displayed moderate to low brain uptakes with little or no specific localization in hippocampal region, where 5-HT1(A) receptors are concentrated. These data indicate that the new iodinated ligands showed high binding affinities and better metabolic stability but displayed unexpectedly low selective binding to 5-HT1(A) receptors in vivo. Additional structural modifications may be needed to correct the unfavorable properties displayed for these iodinated cyclized amide derivatives for in vivo biodistribution in rats.
- Zhuang, Zhi-Ping,Kung, Mei-Ping,Mu, Mu,Kung, Hank F.
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p. 157 - 166
(2007/10/03)
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- Lipase-Catalyzed Preparation of Optically Active γ-Butyrolactones in Organic Solvents
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Lipases in anhydrous organic solvents catalyze the lactonization of esters of γ-hydroxy carboxylic acids with a high degree of stereospecifity.Under these conditions the lipases exhibit both enantioselectivity and prochiral selectivity.We exploited the enzymes' enantioselectivity for synthesis of chiral lactones from racemic γ-hydroxy esters and their prochiral stereospecifity, i.e. the ability to discriminate between enantiotopic groups of a prochiral molecule, for the enantioconvergent lactonization of symmetrical γ-hydroxy diesters.This approach was used to develop a convenient, high yielding, and stereoselective route to several optically active γ-substituted γ-butyrolactones.
- Gutman, Arie L.,Zuobi, Kheir,Bravdo, Tamar
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p. 3546 - 3552
(2007/10/02)
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