- Novel monoacylglycerol lipase inhibitor as well as preparation method and application thereof
-
The invention discloses a novel monoacylglycerol lipase inhibitor as well as a preparation method and application thereof. Specifically, the invention provides a compound shown as a formula I, or a pharmaceutically acceptable salt, a stereoisomer, or a deuterated derivative thereof. Experimental results show that the compound provided by the invention can effectively inhibit MAGL activity, can beused for preparing an MAGL inhibitor and preparing medicines for preventing and/or treating diseases (including endometrial cancer, colorectal cancer, liver cancer, breast cancer, ovarian cancer, neurodegenerative diseases and the like) related to abnormal MAGL activity, and has a wide application prospect.
- -
-
Paragraph 0250-0252
(2021/02/10)
-
- Access to Trisubstituted Fluoroalkenes by Ruthenium-Catalyzed Cross-Metathesis
-
Although the olefin metathesis reaction is a well-known and powerful strategy to get alkenes, this reaction remained highly challenging with fluororalkenes, especially the Cross-Metathesis (CM) process. Our thought was to find an easy accessible, convenient, reactive and post-functionalizable source of fluoroalkene, that we found as the methyl 2-fluoroacrylate. We reported herein the efficient ruthenium-catalyzed CM reaction of various terminal and internal alkenes with methyl 2-fluoroacrylate giving access, for the first time, to trisubstituted fluoroalkenes stereoselectively. Unprecedent TON for CM involving fluoroalkene, up to 175, have been obtained and the reaction proved to be tolerant and effective with a large range of olefin partners giving fair to high yields in metathesis products. (Figure presented.).
- Nouaille, Augustin,Pannecoucke, Xavier,Poisson, Thomas,Couve-Bonnaire, Samuel
-
supporting information
p. 2140 - 2147
(2021/03/06)
-
- Method for synthesizing fluorescent dye intermediate aldehyde by hydroformylation of 1,3-diene compound
-
The invention discloses a method for synthesizing a fluorescent dye intermediate aldehyde by hydroformylation of 1,3-diene compound. The method comprises the following steps: S1, sequentially adding 0.01 mmol (1 mol%) of [Rh(cod)Cl]2, 0.1 mmol of a phosphine ligand(P/Rh=10/1) and 1 mmol of diene into a reaction flask, adding 1 ml of a solvent DMF, putting the reaction flask into a high-pressure reaction kettle, after the reaction is finished, transferring a mixed solution into a 25 mL glass bottle with 200 microliters of n-tridecane as an internal standard by using a rubber head dropper, and detecting; and S2, determining the product yield and the structure through a gas chromatograph and a nuclear magnetic resonance spectrum, wherein the obtained olefin conversion rate is larger than 99%, the aldehyde yield ranges from 61% to 99%, and the regioselectivity of the product aldehyde ranges from 70/30 to 100/0. According to the method disclosed by the invention, the separation and purification steps of aldehyde products are simplified, and the substrate of the dialkene hydroformylation reaction is excellent in universality.
- -
-
Paragraph 0042-0052
(2021/08/07)
-
- Selective Production of Linear Aldehydes and Alcohols from Alkenes using Formic Acid as Syngas Surrogate
-
Performing carbonylation without the use of carbon monoxide for high-value-added products is an attractive yet challenging topic in sustainable chemistry. Herein, effective methods for producing linear aldehydes or alcohols selectively with formic acid as both carbon monoxide and hydrogen source have been described. Linear-selective hydroformylation of alkenes proceeds smoothly with up to 88 % yield and >30 regioselectivity in the presence of single Rh catalyst. Strikingly, introducing Ru into the system, the dual Rh/Ru catalysts accomplish efficient and regioselective hydroxymethylation in one pot. The present processes utilizing formic acid as syngas surrogate operate simply under mild condition, which opens a sustainable way for production of linear aldehydes and alcohols without the need for gas cylinders and autoclaves. As formic acid can be readily produced via CO2 hydrogenation, the protocols represent indirect approaches for chemical valorization of CO2.
- Chen, Junjun,Hua, Kaimin,Liu, Xiaofang,Deng, Yuchao,Wei, Baiyin,Wang, Hui,Sun, Yuhan
-
p. 9919 - 9924
(2021/05/31)
-
- A Simple Nickel Catalyst Enabling an E-Selective Alkyne Semihydrogenation
-
Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom-economic reducing agent dihydrogen (H2), only few catalysts for the challenging E-selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates the E-selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively access E-alkenes employing H2, which could serve as a general method for synthesis.
- Thiel, Niklas O.,Kaewmee, Benyapa,Tran Ngoc, Trung,Teichert, Johannes F.
-
supporting information
p. 1597 - 1603
(2020/02/05)
-
- Acid-catalyzed chirality-transferring intramolecular Friedel-Crafts cyclization of α-hydroxy-α-alkenylsilanes
-
Acid-catalyzed intramolecular Friedel-Crafts cyclization of optically active α-hydroxy-α-alkenylsilanes possessing a benzene ring (>99% ee) with TMSOTf as a Lewis acid gave enantio-enriched tetrahydronaphthalenes (up to 98% ee). The silyl group attached to the chiral carbon played a crucial role in the chirality transfer.
- Sakaguchi, Kazuhiko,Kubota, Shunnichi,Akagi, Wataru,Ikeda, Naoko,Higashino, Masato,Ariyoshi, Shoma,Shinada, Tetsuro,Ohfune, Yasufumi,Nishimura, Takahiro
-
supporting information
p. 8635 - 8638
(2019/07/25)
-
- Remote Functionalization of α,β-Unsaturated Carbonyls by Multimetallic Sequential Catalysis
-
The remote functionalization of α,β-unsaturated carbonyls by an array of multimetallic sequential catalytic systems is described. The reactions are triggered by hydrometalation using [Pd-H] or [Ru-H] isomerization catalysts and driven by the formation of thermodynamically more stable 1,2-vinyl arenes. The Pd-catalyzed deconjugative isomerization was combined with a Cu-catalyzed β-borylation of the transiently generated styrenyl derivatives to deliver a range of products that would not be accessible with the use of a single catalyst. [Pd/Cu] catalytic systems were also identified for the highly enantioselective α-hydroboration and α-hydroamination of the styrenyl intermediates. Difunctionalization simultaneously at the benzylic and homobenzylic positions was achieved by combining the isomerization process with Sharpless asymmetric dihydroxylation (SAD) using [Pd/Os] or [Ru/Os] couples. Starting from a simple α,β-unsaturated ester, an isomerization/dihydroxylation/lactonization sequence gave access to a naturally occurring γ-butyrolactone in good yield, with excellent diastereo- and enantioselectivity.
- Romano, Ciro,Fiorito, Daniele,Mazet, Clément
-
supporting information
p. 16983 - 16990
(2019/10/28)
-
- Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals
-
In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.
- Wu, Fu-Peng,Li, Da,Peng, Jin-Bao,Wu, Xiao-Feng
-
supporting information
p. 5699 - 5703
(2019/08/01)
-
- Radical C(sp2)-H Trifluoromethylation of Aldehydes in Aqueous Solution
-
The copper-mediated C(sp2)-H trifluoromethylation of aldehydes is described. The reaction of aldehydes with (bpy)Cu(CF3)3, Et3SiH, and K2S2O8 in aqueous acetone at room temperatu
- Zhang, Pei,Shen, Haigen,Zhu, Lin,Cao, Weiguo,Li, Chaozhong
-
supporting information
p. 7062 - 7065
(2018/11/21)
-
- Synthesis, in vitro and in silico evaluation of diaryl heptanones as potential 5LOX enzyme inhibitors
-
A new series of diaryl heptanones (12a-q) were synthesized and their structures were confirmed by its 1H, 13C NMR and Mass spectral data. These analogs were evaluated for their anti-oxidant activity and potential to inhibit 5-lipoxygenase. Compounds 12k and 12o showed potent in vitro 5-lipoxygenase enzyme inhibitory activity with IC50 values of 22.2, 21.5 μM, which are comparable to curcumin (24.4 μM). Further they also have shown significant antioxidant activity. Molecular docking studies clearly showed correlation between binding energy and potency of these compounds.
- Meka, Bharani,Ravada, Suryachandra Rao,Muthyala, Murali Krishna Kumar,Kurre, Purna Nagasree,Golakoti, Trimurtulu
-
p. 408 - 421
(2018/07/13)
-
- A Heck-Based Strategy to Generate Anacardic Acids and Related Phenolic Lipids for Isoform-Specific Bioactivity Profiling
-
A synthetic strategy for phenolic lipids such as anacardic acid and ginkgolic acid derivatives using an efficient and selective redox-relay Heck reaction followed by a stereoselective olefination is reported. This approach controls both the alkene position and stereochemistry, allowing the synthesis of natural and unnatural unsaturated lipids as single isomers. By this strategy, the activities of different anacardic acid and ginkgolic acid derivatives have been examined in a matrix metalloproteinase inhibition assay.
- Weigel, William K.,Dennis, Taylor N.,Kang, Amrik S.,Perry, J. Jefferson P.,Martin, David B. C.
-
supporting information
p. 6234 - 6238
(2018/10/05)
-
- Reduction of N,N-Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite
-
A new and concise protocol for selective reduction of N,N-dimethylamides into aldehydes was established using sodium hydride (NaH) in the presence of sodium iodide (NaI) under mild reaction conditions. The present protocol with the NaH-NaI composite allows for reduction of not only aromatic and heteroaromatic but also aliphatic N,N-dimethylamides with wide substituent compatibility. Retention of α-chirality in the reduction of α-enantioriched amides was accomplished. Use of sodium deuteride (NaD) offers a new step-economical alternative to prepare deuterated aldehydes with high deuterium incorporation rate. The NaH-NaI composite exhibits unique chemoselectivity for reduction of N,N-dimethylamides over ketones.
- Chan, Guo Hao,Ong, Derek Yiren,Yen, Zhihao,Chiba, Shunsuke
-
-
- Catalyst-Controlled Diastereoselective Synthesis of Cyclic Amines via C-H Functionalization
-
Reliable regio- and stereochemical techniques applicable to nonactivated aliphatic systems remain largely elusive due to the challenges of discriminating between multiple, relatively strong sp3 C-H bonds whose chemical behavior often differ onl
- Munnuri, Sailu,Adebesin, Adeniyi Michael,Paudyal, Mahesh P.,Yousufuddin, Muhammed,Dalipe, Alfonso,Falck, John R.
-
supporting information
p. 18288 - 18294
(2017/12/27)
-
- Non-imidazole histamine H3 ligands. Part VI. Synthesis and preliminary pharmacological investigation of thiazole-type histamine H3-receptor antagonists with lacking a nitrogen nucleus in the side chain
-
Background: Antagonists to the H3 receptor are considered to be potential drugs for the treatment of Alzheimer's disease, attention deficit-hyperactive disorder, memory and learning deficits, and epilepsy. The initial development of potent H3 receptor antagonists focused on extensive modification of the natural ligand histamine. However, it has appeared that imidazole-containing ligands are associated with inhibition of cytochrome P450 enzymes, caused by imidazole nitrogen complexation to heme iron in the active site of the enzyme. For these reasons, the development of potent non-imidazole H3 receptor antagonists was eagerly awaited. Objective: Previously, we reported the synthesis and pharmacological in vitro characterization of series of potent histamine H3-receptor non-imidazole antagonists belonging to the class of substituted 2-thiazol-4-n-propylpiperazines. A lead compound 1 of this family was a derivative carrying the ethylaminomethylpropyl chain. Methods: With the aim of increasing lipophilicity, that will help the ligands to cross the blood-brain barrier, we synthesized a series of new 2-thiazol-4-n-propylpiperazines where the ethylaminomethylpropyl moiety was replaced by a p-substituted-, an unsubstituted benzene ring, and ω-phenylalkyl substituent at positions 4 and 5 of thiazole ring, respectively. All compounds were tested for H3 antagonistic effects in vitro using the electrically contracting guinea pig jejunum. Results: The most active compounds of presented series 3d, 3e, and 3j showed lower affinity than the lead compound 1 and additionally, derivatives 3d and 3j possessed weak, competitive H1-antagonistic activity. This is in contrast to the lead compound 1 that has no affinity at H1 receptor. Conclusion: We can conclude that a side chain in the 2-thiazol-4-n-propylpiperazine scaffold should contain a basic center and should be present at a favorable position 5 of thiazole ring.
- Guryn, Roman,Staszewski, Marek,Kopczacki, Piotr,Walczyński, Krzysztof
-
-
- Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)
-
The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
- -
-
Page/Page column 98
(2016/06/28)
-
- Development of a potent 2-oxoamide inhibitor of secreted phospholipase A2 guided by molecular docking calculations and molecular dynamics simulations
-
Inhibition of group IIA secreted phospholipase A2 (GIIA sPLA2) has been an important objective for medicinal chemists. We have previously shown that inhibitors incorporating the 2-oxoamide functionality may inhibit human and mouse GIIA sPLA2s. Herein, the development of new potent inhibitors by molecular docking calculations using the structure of the known inhibitor 7 as scaffold, are described. Synthesis and biological evaluation of the new compounds revealed that the long chain 2-oxoamide based on (S)-valine GK241 led to improved activity (IC50 = 143 nM and 68 nM against human and mouse GIIA sPLA2, respectively). In addition, molecular dynamics simulations were employed to shed light on GK241 potent and selective inhibitory activity.
- Vasilakaki, Sofia,Barbayianni, Efrosini,Leonis, Georgios,Papadopoulos, Manthos G.,Mavromoustakos, Thomas,Gelb, Michael H.,Kokotos, George
-
p. 1683 - 1695
(2016/04/05)
-
- General, Simple, and Chemoselective Catalysts for the Isomerization of Allylic Alcohols: The Importance of the Halide Ligand
-
Remarkably simple IrIIIcatalysts enable the isomerization of primary and sec-allylic alcohols under very mild reaction conditions. X-ray absorption spectroscopy (XAS) and mass spectrometry (MS) studies indicate that the catalysts, with the general formula [Cp*IrIII], require a halide ligand for catalytic activity, but no additives or additional ligands are needed.
- Erbing, Elis,Vázquez-Romero, Ana,Bermejo Gómez, Antonio,Platero-Prats, Ana E.,Carson, Fabian,Zou, Xiaodong,Tolstoy, P?ivi,Martín-Matute, Belén
-
supporting information
p. 15659 - 15663
(2016/10/25)
-
- General and Mild Cobalt-Catalyzed C-Alkylation of Unactivated Amides and Esters with Alcohols
-
The borrowing hydrogen or hydrogen autotransfer methodology is an elegant and sustainable or green concept to construct carbon-carbon bonds. In this concept, alcohols, which can be obtained from barely used and indigestible biomass, such as lignocellulose, are employed as alkylating reagents. An especially challenging alkylation is that of unactivated esters and amides. Only noble metal catalysts based on iridium and ruthenium have been used to accomplish these reactions. Herein, we report on the first base metal-catalyzed α-alkylation of unactivated amides and esters by alcohols. Cobalt complexes stabilized with pincer ligands, recently developed in our laboratory, catalyze these reactions very efficiently. The precatalysts can be synthesized easily from commercially available starting materials on a multigram scale and are self-activating under the basic reaction conditions. This Co catalyst class is also able to mediate alkylation reactions of both esters and amides. In addition, we apply the methodology to synthesize ketones and to convert alcohols into aldehydes elongated by two carbon atoms.
- Deibl, Nicklas,Kempe, Rhett
-
p. 10786 - 10789
(2016/09/09)
-
- A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13C-Labeling
-
Terminal alkynes (RCCH) are homologated by a sequence of ruthenium-catalyzed anti-Markovnikov hydration of alkyne to aldehyde (RCH2CHO), followed by Bestmann-Ohira alkynylation of aldehyde to chain-elongated alkyne (RCH2CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of 13C-labeled Bestmann-Ohira reagent (dimethyl ((1-13C)-1-diazo-2-oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply 13C-labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically 13C-labeled products. Terminal alkynes with one or two 13C-labels in the alkyne unit have been submitted to alkyne-azide click reactions; the copper-catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4- over the 1,5-triazine isomer, as shown analytically by 13C NMR spectroscopy.
- Brunner, Andreas,Hintermann, Lukas
-
supporting information
p. 2787 - 2792
(2016/02/27)
-
- Catalytic synergism in a C;inf;60;/inf;IL;inf;10;/inf;TEMPO;inf;2;/inf; hybrid in the efficient oxidation of alcohols
-
A novel fullerene [5:1]hexakisadduct bearing two 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radicals and ten 1-propyl-3-methylimidazolium bromide moieties has been synthesized and characterized. Such an C;inf;60;/inf;IL;inf;10;/inf;TEMPO;inf;2;/inf; hybrid has been successfully employed as a catalyst in the selective oxidation of a wide series of alcohols and is highly active at just 0.1 mol% loading. Moreover, it can be easily recovered by adsorption onto a multilayered covalently-linked SILP phase (mlc-SILP) through a "release and catch" approach and reused for up to 12 cycles without loss in efficiency. Interestingly, a catalytic synergistic effect of TEMPO and imidazolium bromide moieties combined in the same hybrid has been clearly shown.
- Beejapur, Hazi Ahmad,Campisciano, Vincenzo,Giacalone, Francesco,Gruttadauria, Michelangelo
-
supporting information
p. 51 - 58
(2015/01/30)
-
- Oxidative cleavage of allyl ethers by an oxoammonium salt
-
A method to oxidatively cleave allyl ethers to their corresponding aldehydes mediated by an oxoammonium salt is described. Using a biphasic solvent system and mild heating, cleavage proceeds readily, furnishing a variety of α,β-unsaturated aldehydes and ketones.
- Kelly, Christopher B.,Ovian, John M.,Cywar, Robin M.,Gosselin, Taylor R.,Wiles, Rebecca J.,Leadbeater, Nicholas E.
-
supporting information
p. 4255 - 4259
(2015/04/14)
-
- Access to nitriles from aldehydes mediated by an oxoammonium salt
-
A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl-imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.
- Kelly, Christopher B.,Lambert, Kyle M.,Mercadante, Michael A.,Ovian, John M.,Bailey, William F.,Leadbeater, Nicholas E.
-
supporting information
p. 4241 - 4245
(2015/04/14)
-
- SUBSTITUTED BENZOXAZOLONE DERIVATIVES AS ACID CERAMIDASE INHIBITORS, AND THEIR USE AS MEDICAMENTS
-
The present invention relates to substituted benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides substituted benzoxazolone derivatives for use in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.
- -
-
Page/Page column 22; 40; 41; 46; 47
(2015/12/31)
-
- Stable gold(III) catalysts by oxidative addition of a carbon-carbon bond
-
Low-valent late transition-metal catalysis has become indispensable to chemical synthesis, but homogeneous high-valent transition-metal catalysis is underdeveloped, mainly owing to the reactivity of high-valent transition-metal complexes and the challenges associated with synthesizing them. Here we report a carbon-carbon bond cleavage at ambient conditions by a Au(i) complex that generates a stable Au(iii) cationic complex. In contrast to the well-established soft and carbophilic Au(i) catalyst, this Au(iii) complex exhibits hard, oxophilic Lewis acidity. For example, we observed catalytic activation of α,β-unsaturated aldehydes towards selective conjugate additions as well as activation of an unsaturated aldehyde-allene for a [2 + 2] cycloaddition reaction. The origin of the regioselectivity and catalytic activity was elucidated by X-ray crystallographic analysis of an isolated Au(iii)-activated cinnamaldehyde intermediate. The concepts revealed suggest a strategy for accessing high-valent transition-metal catalysis from readily available precursors.
- Wu, Chung-Yeh,Horibe, Takahiro,Jacobsen, Christian Borch,Toste, F. Dean
-
p. 449 - 454
(2015/03/04)
-
- A simple procedure for the oxidation of alcohols using [bis(acetoxy)iodo]benzene and a catalytic amount of bromide ions in ethyl acetate
-
Abstract Primary and secondary benzylic alcohols and secondary aliphatic alcohols were oxidized to the corresponding aldehydes and ketones by using [bis(acetoxy)iodo]benzene (BAIB) and a catalytic amount of bromide ions, from tetrabutylammonium bromide or KBr, in ethyl acetate. The catalytic role of the bromide ions was also highlighted in the oxidation of primary aliphatic alcohols and secondary allylic alcohols carried out in the presence of 1 mol% TEMPO.
- Salvo, Anna Maria Pia,Campisciano, Vincenzo,Beejapur, Hazi Ahmad,Giacalone, Francesco,Gruttadauria, Michelangelo
-
p. 1179 - 1184
(2015/06/02)
-
- CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS
-
Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.
- -
-
Paragraph 0388; 0389
(2014/09/29)
-
- Fullerene as a platform for recyclable TEMPO organocatalysts for the oxidation of alcohols
-
[60]Fullerene has been employed successfully as a molecular platform to anchor 12 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) moieties. Such an octahedrally substituted C60-derivative has been employed as an organocatalyst for the oxidation of primary and secondary alcohols using the Anelli protocol. The reaction showed a general applicability to various alcohols, and the catalyst was recovered easily and could be recycled for at least seven cycles with no loss in catalytic activity. EPR spectroscopy studies revealed that the amount of radicals decreases during the catalytic cycles, even if the recovered material still displays unchanged catalytic activity. This new approach paves the way to use fullerene as a molecular platform to support other kinds of organometallic and organocatalysts as well as for their use as model compounds to understand the behavior of other nanocarbon-supported catalysts.
- Beejapur, Hazi Ahmad,Campisciano, Vincenzo,Franchi, Paola,Lucarini, Marco,Giacalone, Francesco,Gruttadauria, Michelangelo
-
p. 2419 - 2424
(2014/08/18)
-
- A stereoselective aldol approach for the total syntheses of two 6-Alkylated 2H-pyran-2-ones
-
A simple and highly efficient stereoselective total synthesis of the 6-alkylated pyranones (6R)-6-[(1E,4R,6R)-4,6-dihydroxy-10-phenyldec-1-en-1-yl]- 5,6-dihydro-2H-pyran-2-one (1) and (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6- phenylhexyl]-2H-pyran-2-one (2) w
- Rajaram, Singanaboina,Ramesh, Dasari,Ramulu, Udugu,Prabhakar, Peddikotla,Venkateswarlu, Yenamandra
-
p. 112 - 121
(2014/02/14)
-
- An efficient partial reduction of α,β-unsaturated esters using DIBAL-H in flow
-
The partial reduction of α,β-unsaturated esters and benzoate derivatives to form the corresponding aldehydes was achieved using a flow reactor system within 1 s at a high flow rate (18 mL min-1) under cryogenic conditions (-97°C). Commercially available diisobutylaluminium hydride (DIBAL-H) was used as the reductant. The desired enals and benzaldehyde derivatives, except for 4-methoxycinnamate and 4-methoxybenzoate, were formed selectively and redox economically in moderate to high yields.
- Yoshida, Masahito,Otaka, Hiroyuki,Doi, Takayuki
-
p. 6010 - 6016
(2015/03/30)
-
- Palladium on charcoal as a catalyst for stoichiometric chemo- and stereoselective hydrosilylations and hydrogenations with triethylsilane
-
Stoichiometric quantities of triethylsilane in the presence of activated Pd/C as the catalyst can be used to effect chemo-, regio-, and stereoselective hydrosilylation and transfer hydrogenation reactions. α,β-Unsaturated aldehydes and ketones are selectively hydrosilylated to give the corresponding enol silanes or transfer hydrogenated to give the saturated carbonyl compounds in the presence of other reducible functional groups.
- Tuokko, Sakari,Pihko, Petri M.
-
p. 1740 - 1751
(2015/02/19)
-
- Synthesis and structure-activity relationship (SAR) of 2-methyl-4-oxo-3- oxetanylcarbamic acid esters, a class of potent N-acylethanolamine acid amidase (NAAA) inhibitors
-
N-Acylethanolamine acid amidase (NAAA) is a lysosomal cysteine hydrolase involved in the degradation of saturated and monounsaturated fatty acid ethanolamides (FAEs), a family of endogenous lipid agonists of peroxisome proliferator-activated receptor-α, which include oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). The β-lactone derivatives (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide (2) and (S)-N-(2-oxo-3-oxetanyl)- biphenyl-4-carboxamide (3) inhibit NAAA, prevent FAE hydrolysis in activated inflammatory cells, and reduce tissue reactions to pro-inflammatory stimuli. Recently, our group disclosed ARN077 (4), a potent NAAA inhibitor that is active in vivo by topical administration in rodent models of hyperalgesia and allodynia. In the present study, we investigated the structure-activity relationship (SAR) of threonine-derived β-lactone analogues of compound 4. The main results of this work were an enhancement of the inhibitory potency of β-lactone carbamate derivatives for NAAA and the identification of (4-phenylphenyl)-methyl-N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]carbamate (14q) as the first single-digit nanomolar inhibitor of intracellular NAAA activity (IC50 = 7 nM on both rat NAAA and human NAAA).
- Ponzano, Stefano,Bertozzi, Fabio,Mengatto, Luisa,Dionisi, Mauro,Armirotti, Andrea,Romeo, Elisa,Berteotti, Anna,Fiorelli, Claudio,Tarozzo, Glauco,Reggiani, Angelo,Duranti, Andrea,Tarzia, Giorgio,Mor, Marco,Cavalli, Andrea,Piomelli, Daniele,Bandiera, Tiziano
-
supporting information
p. 6917 - 6934
(2013/10/01)
-
- DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)
-
The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.
- -
-
Paragraph 0277
(2013/06/06)
-
- Efficient synthesis of a new series of piperidine ring-modified analogs of (±)-threo-methyl phenyl(piperidin-2-yl)acetate
-
A series of novel piperidine ring modified analogs of (±)-threo- methyl phenyl (piperidin-2-yl)acetate was synthesized by direct alkylation and reductive amination procedure, using sodium borohydride over molecular sieves. The chemical structures of these compounds were established based on mass spectra, 1H NMR spectra, and CHN elemental analysis data. Several significant modifications in the literature methodologies were made to make the reaction more efficient, and good yields were generally obtained. Copyright Taylor & Francis Group, LLC.
- Ojo, Babatunde
-
experimental part
p. 1731 - 1745
(2012/06/29)
-
- An asymmetric hydroformylation catalyst that delivers branched aldehydes from alkyl alkenes
-
Surprising selectivity: The first enantioselective hydroformylations of simple alkenes of type RCH2CH=CH2 to preferentially deliver the branched aldehyde product have been discovered using a new chiral ligand, named bobphos (see scheme). Established ligands are unselective in this reaction or show a slight preference towards the linear aldehyde. Copyright
- Noonan, Gary M.,Fuentes, Jose A.,Cobley, Christopher J.,Clarke, Matthew L.
-
supporting information; experimental part
p. 2477 - 2480
(2012/04/18)
-
- Ion-pair complexation with a cavitand receptor
-
The capability of resorcinarenes to bind anions within the alkyl feet at the lower rim has been exploited as the starting point for developing a new cavitand able to engulf contact ion pairs of primary ammonium salts in chlorinated solvents with association constants (Kass) in the range of 103104M-1. Methylene bridges were introduced into the upper rim to freeze the resorcinarene in the cone conformation with the four Hdown protons converging in the lower pocket, thereby maximizing the CH-anion interactions responsible for the anion binding. Four additional phosphate moieties were introduced into the lower rim in close prox-imity to the anionic site to provide hydrogen-bonding-acceptor P=O groups and promote cation complexation at the bottom of the cavitand. The binding ability of the synthesized ligands was analyzed by 1H NMR spectroscopy and, when possible, by isothermal titration calorimetry (ITC); the data were in agreement when complementary techniques were used.
- Tancini, Francesca,Gottschalk, Thomas,Bernd Schweizer,Diederich, Francois,Dalcanale, Enrico
-
experimental part
p. 7813 - 7819
(2010/09/05)
-
- Double diastereoselective, nucleophile-catalyzed aldol lactonizations (NCAL) leading to β-lactone fused carbocycles and extensions to β-lactone fused tetrahydrofurans
-
A double diastereoselective variant of the nucleophile-catalyzed aldol lactonization (NCAL) process is described. This strategy delivers β-lactone-fused carbocycles with good to excellent diastereoselectivities using cinchona alkaloid catalysts with enantioenriched aldehyde acids, which gave low diastereoselectivity based on substrate control alone. β-Lactone-fused tetrahydrofurans are also prepared for the first time via the NCAL process; however, diastereoselectivity was only modestly improved when applying double diastereodifferentiation to these systems.
- Morris, Kay A.,Arendt, Kevin M.,Oh, Seong Ho,Romo, Daniel
-
supporting information; experimental part
p. 3764 - 3767
(2010/11/04)
-
- Combined transition-metal- and organocatalysis: An atom economic C3 homologation of alkenes to carbonyl and carboxylic compounds
-
A combination of regioselective room-temperature/ambient-pressure hydroformylation (transitionmetal catalysis) and decarboxylative Knoevenagel reactions (organocatalysis) allowed for the development of an efficient, one-pot C3 homologation of terminal alkenes to (E)-α,β-unsaturated acids and esters, (E)-β,γ-unsaturated acids, (E)-α-cyano acrylic acids, and α,β-unsaturated nitriles. All reactions proceed under mild conditions, tolerate a variety of functional groups, and furnish unsaturated carbonyl compounds in good yields and with excellent regioand stereocontrol. Further, an iterative C2 homologation of (E)-α,β-unsaturated carboxylic acids is possible through a combination of decarboxylative hydroformylation employing a supramolecular catalyst followed by decarboxylative Knoevenagel condensation with an organocatalyst.
- Kemme, Susanne T.,Smejkal, Tomas,Breit, Bernhard
-
supporting information; experimental part
p. 3423 - 3433
(2010/06/21)
-
- Enantioselective linchpin catalysis by SOMO catalysis: An approach to the asymmetric a-chlorination of aldehydes and terminal epoxide formation
-
Time for SOme MOre: For the first time SOMO (singly occupied molecular orbital) activation has been exploited to allow a new approach to the α-chlorination of aldehydes. This transformation can be readily implemented as part of a linchpin catalysis approach to the enantioselective production of terminal epoxides.
- Amatore, Muriel,Beeson, Teresa D.,Brown, Sean P.,MacMillan, David W. C.
-
supporting information; experimental part
p. 5121 - 5124
(2009/12/07)
-
- Practical synthesis of (E)-α,β-unsaturated carboxylic acids using a one-pot hydroformylation/decarboxylative Knoevenagel reaction sequence
-
Combining the regioselective room temperature/ambient pressure hydroformylation and a modification of the Doebner-Knoevenagel reaction allowed for the development of an efficient, one-pot procedure for the synthesis of (E)-α,β-unsaturated carboxylic acids. The reaction proceeds under mild conditions, tolerates a variety of functional groups and gives (E)-α,β-unsaturated carboxylic acids in good yields and with excellent regio-and stereocontrol. The practicability of this process has been demonstrated by a short protecting group-free synthesis of the queen honeybee pheromones 9-ODA[( E)-9-oxodec-2-enoic acid] and 9-HDA[( E)-9-hydroxydec-2-enoic acid].
- Kemme, Susanne T.,?mejkal, Tomá?,Breita, Bernhard
-
supporting information; experimental part
p. 989 - 994
(2009/05/27)
-
- First stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran- 2-one
-
A stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran- 2-one is reported. The strategy utilizes an iterative Jacobsen hydrolytic kinetic resolution, ring opening with a chiral propargylic synthon and
- Radha Krishna, Palakodety,Srinivas, Ravula
-
p. 2013 - 2015
(2007/10/03)
-
- Hydroformylation of olefins catalyzed by rhodium complexes with phosphinitecalix[4]arenes
-
Hydroformylation of alkenes with various carbon chain lengths and arylalkenes in the presence of the catalytic system consisting of Rh(acac)(CO)2 and phosphinitecalix[4]arenes was studied. The influence of the P/Rh and substrate/catalyst ratios, temperature, and pressure on the process and the product composition was examined.
- Karakhanov,Kardasheva,Runova,Terenina,Shadrova
-
p. 340 - 344
(2008/09/17)
-
- Microwave-assisted generation of alkoxyl radicals and their use in additions, β-fragmentations, and remote functionalizations
-
Microwave irradiation (2.45 GHz, 300-500 W) of N-(alkoxy)thiazole-2(3H)- thiones in low-absorbing solvents affords alkoxyl radicals, which were identified by (i) spin adduct formation (EPR-spectroscopy) and (ii) fingerprint-type selectivities in intramolecular additions (stereoselective synthesis of disubstituted tetrahydrofurans), β-fragmentations (formation of carbonyl compounds), and C,H-activation of aliphatic subunits, by δ-selective hydrogen atom transfer. C-Radicals formed from oxygen-centered intermediates were trapped either by Bu3SnH, l-cysteine ethyl ester, the reduced form of glutathione (reductive trapping), or by bromine atom donor BrCCl3 (heteroatom functionalization) The results suggest that microwave activation is superior to UV/Vis-photolysis and conductive heating for alkoxyl radical generation from N-(alkoxy)thiazolethiones. It offers by far the shortest reaction times along with the option to reduce the amount of trapping reagent significantly. The Royal Society of Chemistry 2006.
- Hartung, Jens,Daniel, Kristina,Gottwald, Thomas,Gross, Andreas,Schneiders, Nina
-
p. 2313 - 2322
(2008/02/08)
-
- Soluble and insoluble polymeric 1,3-dithiane reagents for the synthesis of aldehydes from alkyl halides
-
Through the synthesis and study of model systems as proper dithiane derivatives, vinyl monomers and soluble copolymeric reagents containing 2-unsubstituted 1,3-dithiane rings, we attained the key synthon 1,3-dithiane-5-methanol. Through its reaction with commercial resins, new polymeric reagents useful for supported organic synthesis and combinatorial chemistry were developed. Exploiting the reactivity of position 2 in 1,3-dithiane rings, such polymeric reagents were employed in the production of aldehydes from alkyl halides through a process entirely free from unpleasant odors.
- Bertini, Vincenzo,Lucchesini, Francesco,Pocci, Marco,Alfei, Silvana
-
p. 9519 - 9526
(2007/10/03)
-
- Strategies for the generation of molecularly imprinted polymeric nitroxide catalysts
-
(Chemical Equation Presented) Two strategies for preparing catalytically active molecularly imprinted nitroxide-containing polymers are outlined. Both strategies rely upon the thermal rearrangement chemistry of tertiary amine N-oxides. To this end, several polymers were prepared and the polymeric nitroxides were revealed by oxidation with m-CPBA. All of the resulting polymeric catalysts proved to be competent mediators of the oxidation of alcohols.
- Anderson, Christopher D.,Shea, Kenneth J.,Rychnovsky, Scott D.
-
p. 4879 - 4882
(2007/10/03)
-
- Rhodium-catalyzed cascade reactions: A methylenation-hydroboration homologative process
-
A very efficient rhodium-catalyzed cascade process allowing the transformation of aldehydes and ketones into their corresponding one or two-carbon homologated alcohol products through a methylenation-hydroboration sequence is reported. Wilkinson's complex is used to catalyze both reactions in a one-pot procedure that does not require the isolation of the alkene intermediate.
- Lebel, Hélène,Ladjel, Chehla
-
p. 5198 - 5205
(2007/10/03)
-
- The first stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2- hydroxy-6-phenylhexyl]-2H-pyran-2-one
-
Iterative asymmetric allylations and ring-closing metathesis have been effectively performed for the first stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one, a novel α,β-unsaturated-δ-lactone having antifu
- Chandrasekhar,Narsihmulu, Ch.,Sultana, S. Shameem,Srinivasa Reddy
-
p. 9299 - 9301
(2007/10/03)
-
- TEMPO-mediated environmentally benign oxidation of primary alcohols to carboxylic acids with poly[4-(diacetoxyiodo)styrene]
-
An operationally simple and environmentally benign oxidation of primary alcohols to the corresponding carboxylic acids with a TEMPO-mediated poly[4-(diacetoxyiodo)styrene] system in acetone and water was carried out.
- Tashino, Yousuke,Togo, Hideo
-
p. 2010 - 2012
(2007/10/03)
-
- Synthesis and preliminary pharmacological evaluation of 4′-arylalkyl analogues of clozapine. II. Effect of the nature and length of the linker
-
We report the synthesis of a second generation of tricyclic analogues of clozapine, investigating the length and nature of the chain between an ionizable nitrogen atom at physiological pH and the introduced aryl moiety. The chemistry, structural characterization, and pharmacological evaluation of this series of 4′-arylalkyl analogues of clozapine are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and type of aryl moiety on blockade of dopamine D4 and serotonin 5-HT2A receptors are discussed and animal behavioural data for key compounds presented.
- Capuano, Ben,Crosby, Ian T.,Lloyd, Edward J.,Podloucka, Anna,Taylor, David A.
-
p. 875 - 886
(2007/10/03)
-
- Chromium(VI) supported and entrapped on silica and zirconia as recyclable materials for oxidation of alcohols
-
Oxidation of alcohols have been realized with Cr(VI) oxide supported or entrapped, via sol-gel methodology, on silica and zirconia. These materials were easily recovered from the reaction mixture without leaching of chromium in solution. Moreover, recycling studies have indicated that they can be regenerated by calcinations at 400-600°C or by treatment with ozone at room temperature. In the case of Cr(VI) entrapped into silica matrix up to 18 oxidation cycles have been realized without loss in activity.
- Gruttadauria, Michelangelo,Liotta, Leonarda F.,Deganello, Giulio,Noto, Renato
-
p. 4997 - 5002
(2007/10/03)
-
- Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines
-
A series of 6-aralkyl substituted 2,4-diaminothieno[2,3-d]pyrimidines in which the 6-aryl group is separated from the thieno[2,3-d]pyrimidine ring by two to five methylene groups were synthesized and studied as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds in which the thieno[2,3-d]pyrimidine ring is separated from the 6-aryl substituent by three methylene groups were the most potent inhibitors of the series (with IC50 values ranging from 0.24 and 11.0 μM) but those with two methylene groups between the aromatic rings were the most selective agents.
- Donkor, Isaac O.,Li, Hui,Queener, Sherry F.
-
p. 605 - 611
(2007/10/03)
-