14209-41-7Relevant academic research and scientific papers
Design and pharmacology of quinuclidine derivatives as M2-selective muscarinic receptor ligands
Boehme, Thomas M.,Keim, Christine,Dannhardt, Gerd,Mutschler, Ernst,Lambrecht, Guenter
, p. 1241 - 1243 (2001)
In our search for M2-selective muscarinic receptor antagonists, we synthesized 1,3-disubstituted indenes. The effects of different basic moieties with regard to binding and selectivity towards the five distinct muscarinic receptor subtypes were investigated. The results show that the quinuclidine series afforded the most promising compounds in terms of both receptor affinity and M2-subtype selectivity.
Synthesis of 1-fluoroindan-1-carboxylic acid (FICA) and its properties as a chiral derivatizing agent
Takahashi, Tamiko,Kameda, Hiroaki,Kamei, Tomoyo,Ishizaki, Miyuki
, p. 760 - 768 (2006)
1-Fluoroindan-1-carboxylic acid (FICA) (1) was designed and synthesized as its methyl ester (FICA Me ester) (4) in order to develop an efficient chiral derivatizing agent (CDA) which excels α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) in capability. FICA Me ester (4) was prepared by fluorination of methyl 1-hydroxyindan-1-carboxylate (3) with (diethylamino)sulfur trifluoride (DAST) and derived to the esters of racemic secondary alcohols by ester exchange reaction. The resulting ΔδF value was large in the case of 2-butyl ester of FICA (5a), whereas not detectable in the case of the corresponding MTPA ester (6a). The magnitude of the ΔδH values was similar to that of MTPA esters. The diastereomers of (R)-(-)-8-phenylmenthyl ester of FICA (5i) was separated and their 1H NMR analyses revealed that the concept of the modified Mosher's method was successfully applied to 5i.
Photoenzymatic Reductions Enabled by Direct Excitation of Flavin-Dependent "Ene"-Reductases
Sandoval, Braddock A.,Clayman, Phillip D.,Oblinsky, Daniel G.,Oh, Seokjoon,Nakano, Yuji,Bird, Matthew,Scholes, Gregory D.,Hyster, Todd K.
supporting information, p. 1735 - 1739 (2021/01/25)
Non-natural photoenzymatic reactions reported to date have depended on the excitation of electron donor-acceptor complexes formed between substrates and cofactors within protein active sites to facilitate electron transfer. While this mechanism has unlocked new reactivity, it limits the types of substrates that can be involved in this area of catalysis. Here we demonstrate that direct excitation of flavin hydroquinone within "ene"-reductase active sites enables new substrates to participate in photoenzymatic reactions. We found that by using photoexcitation these enzymes gain the ability to reduce acrylamides through a single electron transfer mechanism.
Erratum: Photoenzymatic Reductions Enabled by Direct Excitation of Flavin-Dependent 'Ene'-Reductases (J. Am. Chem. Soc. (2021) 143:4 (1735-1739) DOI: 10.1021/jacs.0c11494)
Sandoval, Braddock A.,Clayman, Phillip D.,Oblinsky, Daniel G.,Oh, Seokjoon,Nakano, Yuji,Bird, Matthew,Scholes, Gregory D.,Hyster, Todd K.
supporting information, p. 3662 - 3662 (2021/04/09)
Support by the Department of Energy was inadvertently left out of the Acknowledgments and a coauthor's name was misspelled in the Supporting Information. The scientific part of the manuscript remains unchanged. The complete correct Acknowledgment paragraph is as follows.
From Carbodiimides to Carbon Dioxide: Quantification of the Electrophilic Reactivities of Heteroallenes
Li, Zhen,Mayer, Robert J.,Ofial, Armin R.,Mayr, Herbert
supporting information, p. 8383 - 8402 (2020/05/22)
Kinetics of the reactions of isocyanates, isothiocyanates, carbodiimides, carbon disulfide, and carbon dioxide with carbanions or enamines (reference nucleophiles) have been measured photometrically in acetonitrile or DMSO solution at 20 °C. The resulting second-order rate constants and the previously published reactivity parameters N and sN of the reference nucleophiles were substituted into the correlation log k2(20 °C) = sN(N + E) to determine the electrophilicity parameters of the heteroallenes: TsNCO (E = -7.69) ? PhNCO (E = -15.38) > CS2 (E = -17.70) ≈ PhNCS (E = -18.15) > PhNCNPh (E = -20.14) ? CyNCNCy (E ≈ -30). An approximate value could be derived for CO2 (-16 E - 11). Quantum chemical calculations were performed at the IEFPCM(DMSO)/B3LYP-D3/6-311+G(d,p) level of theory and compared with experimental Gibbs activation energies. The distortion-interaction model was used to rationalize the different reactivities of O- and S-substituted heteroallenes. Eventually it is demonstrated that the electrophilicity parameters determined in this work can be used as ordering principle for literature-known reactions of heteroallenes.
Gold(I)/Xiang-Phos-Catalyzed Asymmetric Intramolecular Cyclopropanation of Indenes and Trisubstituted Alkenes
Zhang, Pei-Chao,Wang, Yidong,Zhang, Zhan-Ming,Zhang, Junliang
supporting information, p. 7049 - 7052 (2018/11/24)
The first intramolecular enantioselective cyclopropanation of indenes and trisubstituted alkenes was accomplished by using new chiral phosphine X5 derived gold(I) complexes. This reaction is a straightforward, efficient method for constructing [5-3-6] fused-ring compounds with two vicinal all-carbon quaternary stereogenic centers, a core structure shared by numerous pharmacological products, and bioactive compounds. The salient features of this transformation include high enantioselectivity (up to >98% ee), excellent yield (>97%), and nice functional group tolerance.
Dynamic enzymatic kinetic resolution of methyl 2,3-dihydro-1h-indene-1- carboxylate
Pietruszka, Joerg,Simon, Robert Christian,Kruska, Fabian,Braun, Manfred
experimental part, p. 6217 - 6224 (2010/03/26)
A new reaction setup for kinetic enzymatic resolution was established and is demonstrated for the case of the hydrolase-catalysed conversion of methyl 2,3-dihydro-1H-indene1-carboxylate (1) in conjunction with a base-catalysed racemisation. The system allows controlled racemisation, resulting in efficient dynamic kinetic resolution (DKR) of the title compound. Short reaction times and high enantio-selectivities were obtained with CAL-B and TBD (1,5,7-triazabicyclo[4,4.0]dec-5-ene). Compound (R)-1 (ee 95%) served as a starting material in a domino reaction that led to the biaryl indanyl ketone (R)-8, a lead compound for novel inhibitors of peptidyl-prolyl-cis/irans- isomerases, in 94 % ee. Wiley-VCH Verlag GmbH & Co. KGaA,.
Kinetics and mechanism of the isomerization of 1H-indene-1-carboxylic acid to 1H-indene-3-carboxylic acid in aqueous solution and determination of their keto-enol equilibrium constants and acid dissociation constants of the keto and enol forms. Implication on the photolysis of diazonaphthoquinones
Andraos,Kresge,Popik
, p. 961 - 967 (2007/10/02)
Rates of isomerization of 1H-indene-1-carboxylic acid to 1H-indene-3-carboxylic acid were measured in dilute aqueous solutions of HClO4, NaOH, and CH3CO2H and H2PO4-, (CH3)3CPO3H-, and HCO3- buffers. This gave a rate profile which, together with the occurrence of general base catalysis and sizable primary kinetic isotope effects, indicates that the isomerization takes place through an enolization-reketonization reaction sequence. The equilibrium constant of the isomerization reaction is K = [indene-3-carboxylic acid]/[indene-1-carboxylic acid] = 200 in aqueous acid solution and K = 100 in base. The ratio of products formed by ketonization of the indenecarboxylic acid enol intermediate generated in the photolysis of 2-diazo-1 (2H)-naphthalenone is R = [indene-3-carboxylic acid]/[indene-1-carboxylic acid] = 0.47 in aqueous acid solution and R = 20 in base. The failure of previous investigations of the photolysis reaction to detect any indene-1-carboxylic acid as the product is attributed to the facile isomerization of this substance to indene-3-carboxylic acid and the preponderance of the latter at equilibrium. The enol intermediate of this isomerization reaction was also generated by flash photolysis of 2-diazo-1 (2H)-naphthalene and rates of its ketonization were measured in dilute aqueous HClO4 solutions. Analysis of the data gave the enol acidity constant pKaE = 2.09. The results, in combination with those for the isomerization reaction, also provided carbon acid acidity constants (KaK) and keto-enol equilibrium constants (KE) for the two acids: pKaK = 9.35 and pKE = 7.26 for indene-1-carboxylic acid and pKaK = 11.69 and pKE = 9.60 for indene-3-carboxylic acid.
Flash photolysis of α-diazonaphthoquinones in aqueous solution: Determination of rates and equilibria for keto-enol tautomerization of 1-indene-3-carboxylic acid
Almstead, Ji-In Kim,Urwyler, Bernhard,Wirz, Jakob
, p. 954 - 960 (2007/10/02)
Flash photolysis of either 1-diazo-2(1H)naphthalenone (1a) or 2-diazo-1(2H)naphthalenone (1b) generates benzofulven-8-one (2). Hydrolysis of ketene 2 forms benzofulvene-8,8-diol (3), the enol tautomer of indene-3-carboxylic acid (4). pH rate profiles for the reactions 2 → 3 and 3 → 4 were determined in aqueous solution. Ketonization of 3 is catalyzed by acid and by base. Catalysis by protons saturates in strongly acidic solutions, thereby defining the first ionization constant of the enol, pKaE = 1.90 ± 0.05, catalysis by hydroxyl ions saturates in dilute base, defining the second ionization constant, pK′aE = 8.3 ± 0.2. The first (OH) and second (CH) ionization constants of 4 were determined by spectrophotometric titration, pKaK = 4.50 ± 0.03 and pK′aK = 15.2 ± 0.2. Two independent estimates of the enolization constants of 4 and 4-, the first based on thermodynamic cycles, the second on the ratio of enolization and ketonization rates, were combined to give pKE = 9.3 ± 0.3, pK′E = 6.6 ± 0.3. Ketene 2 is formed by irradiation of 1-bromo-2-naphthol at 12 K in an argon matrix, but neither it nor its isomer 2-bromo-1-naphthol were suitable for the generation and observation of 2 and 3 by flash photolysis in aqueous solution.
Non-competitive NMDA receptor antagonists and methods for their use
-
, (2008/06/13)
The present invention relates to novel NMDA receptor antagonists and methods for their use. The present invention also provided pharmaceutical compositions comprising such NMDA receptor antagonists.
