- Novel Pyridine-Based Hydroxamates and 2′-Aminoanilides as Histone Deacetylase Inhibitors: Biochemical Profile and Anticancer Activity
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Starting from the N-hydroxy-3-(4-(2-phenylbutanoyl)amino)phenyl)acrylamide (5 b) previously described by us as a HDAC inhibitor, we prepared four aza-analogues, 6–8, 9 b, as regioisomers containing the pyridine nucleus. Preliminary screening against mHDAC1 highlighted the N-hydroxy-5-(2-(2-phenylbutanoyl)amino)pyridyl)acrylamide (9 b) as the most potent inhibitor. Thus, we further developed both pyridylacrylic- and nicotinic-based hydroxamates (9 a, 9 c–f, and 11 a–f) and 2′-aminoanilides (10 a–f and 12 a–f), related to 9 b, to be tested against HDACs. Among them, the nicotinic hydroxamate 11 d displayed sub-nanomolar potency (IC50: 0.5 nM) and selectivity up to 34 000 times that of HDAC4 and from 100 to 1300 times that of all the other tested HDAC isoforms. The 2′-aminoanilides were class I-selective HDAC inhibitors, generally more potent against HDAC3, with the nicotinic anilide 12 d being the most effective (IC50HDAC3=0.113 μM). When tested in U937 leukemia cells, the hydroxamates 9 e, 11 c, and 11 d blocked over 80 % of cells in G2/M phase, whereas the anilides did not alter cell-cycle progress. In the same cell line, the hydroxamate 11 c and the anilide 10 b induced about 30 % apoptosis, and the anilide 12 c displayed about 40 % cytodifferentiation. Finally, the most potent compounds in leukemia cells 9 b, 11 c, 10 b, 10 e, and 12 c were also tested in K562, HCT116, and A549 cancer cells, displaying antiproliferative IC50 values at single-digit to sub-micromolar level.
- Zwergel, Clemens,Di Bello, Elisabetta,Fioravanti, Rossella,Conte, Mariarosaria,Nebbioso, Angela,Mazzone, Roberta,Brosch, Gerald,Mercurio, Ciro,Varasi, Mario,Altucci, Lucia,Valente, Sergio,Mai, Antonello
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p. 989 - 999
(2020/12/17)
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- Isothiourea-Catalyzed Acylative Kinetic Resolution of Tertiary α-Hydroxy Esters
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A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous-flow process using a polymer-supported variant of the catalyst.
- Greenhalgh, Mark D.,Laina-Martín, Víctor,Neyyappadath, Rifahath M.,Qu, Shen,Smith, Andrew D.,Smith, Samuel M.
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p. 16572 - 16578
(2020/09/09)
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- Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C–H Acetoxylation and Alkenylation of Arylacetamides
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The 2-(neopentylsulfinyl)aniline directing group that promotes rapid palladium-catalyzed C–H acetoxylation and alkenylation of arylacetamides has been developed. The acetoxylation reaches completion within only 40 min at 100 °C and leads to the bis-functionalized products. Alternatively, the reaction can be carried out at room temperature, which is beneficial for sensitive substrates. For the alkenylation, we have developed a protocol in which easily available 1-substituted cyclopropanols were employed as equivalents of vinyl ketones.
- Barysevich, Maryia V.,Laktsevich-Iskryk, Marharyta V.,Krech, Anastasiya V.,Zhabinskii, Vladimir N.,Khripach, Vladimir A.,Hurski, Alaksiej L.
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supporting information
p. 937 - 943
(2020/02/25)
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- Visible-Light-Assisted Gold-Catalyzed Fluoroarylation of Allenoates
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A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β-fluoroalkyl-containing cinnamate derivatives. The reaction proceeds through visible-light-promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio- and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.
- Feng, Chao,Tang, Hai-Jun,Zhang, Xinggui,Zhang, Yu-Feng
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supporting information
p. 5242 - 5247
(2020/02/28)
-
- Forming All-Carbon Quaternary Stereocenters by Organocatalytic Aminomethylation: Concise Access to β2,2-Amino Acids
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The asymmetric synthesis of β2,2-amino acids remains a formidable challenge in organic synthesis. Here a novel organocatalytic enantioselective aminomethylation of ketenes with stable and readily available N,O-acetals is reported, providing β2,2-amino esters bearing an all-carbon quaternary stereogenic center in high enantiomeric ratios with a catalytic amount of chiral phosphoric acid. Typically, this transformation probably proceeds through an asymmetric counter-anion-directed catalysis. As a result, a concise, practical, and atom-economic protocol toward rapidly access to β2,2-amino acids has been developed.
- Shao, Ying,Sun, Jiangtao,Tang, Shengbiao,Wang, Kai,Yu, Jianliang
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supporting information
p. 23516 - 23520
(2020/10/21)
-
- Synthesis and in vitro anti-platelet aggregation activities of 2-methoxy-5-arylamido-N-(pyridin-3-yl-methyl)benzamides
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In order to discover novel compounds with anti-platelet aggregation activities, a series of novel 2-methoxy-5-arylamido-N-(pyridin-3-ylmethyl)benzamides (1a–n) were synthesized and their anti-platelet aggregation activities were evaluated by the turbidimetric method in response to the following agonists: adenosine diphosphate (ADP) (5 mM/L), arachidonic acid (AA) (20 μM/L), and collagen (1 mg/mL). Those synthesized compounds that have better in vitro activities were subjected to cell toxicity tests via cell counting kit-8 (CCK-8) assay. The biological evaluation revealed that compound 1a (IC50: 0.21 μM/L) exhibited the highest anti-platelet aggregation activities when ADP was selected as an inducer, and compound 1b (IC50: 0.23 μM/L) showed the best activities when AA was selected as inducer, and compound 1m (inhibition rate: 55.06%) had significant anti-platelet aggregation activities when collagen was selected as inducer among all target compounds. Moreover, the effect of cell toxicity exhibited that none of the compounds had obvious cell toxicity against L929 cells. Therefore, 2-methoxy-5-arylamido-N-(pyridin-3-ylmethyl)benzamides have the potential to become a novel kind of anti-platelet drugs and deserve further study.
- Wang, Yan,Wang, Xiao,Chen, Xin,Liu, Xiujie
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- Palladium-catalyzed α,β-dehydrogenation of acyclic ester equivalents promoted by a novel electron deficient phosphinooxazoline ligand
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A unique example of Pd-catalyzed decarboxylative dehydrogenation of fully substituted N-acyl allyl enol carbonates is enabled by a new electron deficient phosphinooxazoline (PHOX) ligand. The reaction proceeds from the Z-enol carbonate to provide dehydrogenation products exclusively in high E/Z selectivity, while the E-enol carbonate provides the α-allylation product with only minor dehydrogenation. The reaction proceeds with a broad scope of Z-enol carbonates derived from N-acyl indoles to furnish acyclic formal α,β-unsaturated ester equivalents.
- Fulton, Tyler J.,Wu, Brenda,Alexy, Eric J.,Zhang, Haiming,Stoltz, Brian M.
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supporting information
p. 4104 - 4109
(2019/06/20)
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- Carboxamides as N-Alkylating Reagents of Secondary Amines in Indium-Catalyzed Reductive Amination with a Hydrosilane
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A method for the catalytic reductive N-alkylation of amines by using secondary amides as the alkyl source was developed. A versatile type of carboxamide functioned as an N-alkylation reagent in the presence of an indium(III) catalyst and a hydrosilane to provide alkylated tertiary amines efficiently. This amide-based catalytic N-alkylation strategy is considered to be a highly useful protocol to access unsymmetrical tertiary amines.
- Ogiwara, Yohei,Shimoda, Wataru,Ide, Keisuke,Nakajima, Takumi,Sakai, Norio
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supporting information
p. 2866 - 2870
(2017/06/06)
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- Bidentate ligand 8-aminoquinoline-aided Pd-catalyzed diastereoselective β-arylation of the prochiral secondary sp3 C-H bonds of 2-phenylbutanamides and related aliphatic carboxamides
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Investigations on the Pd-catalyzed 8-aminoquinoline-aided diastereoselective β-arylation of the prochiral 2° sp3 C-H bonds of various aliphatic carboxamides having substituents at the α- or γ-positions are reported. The Pd-catalyzed β-arylation of the 2° sp3 C-H bonds of racemic 2-phenylbutanamides with aryl iodides gave the arylated products (±)-3a-l (anti isomers) with moderate to good diastereoselectivities (dr up to 86:14). Next, the Pd-catalyzed β-arylation of various γ-substituted aliphatic carboxamides with aryl iodides furnished the corresponding C-H arylated products with poor diastereoselectivities. Then, the arylation of the C(β)-H bonds of 2-ethyl-N-(quinolin-8-yl)butanamide possessing two prochiral centers with aryl iodides successfully furnished the bis arylated products meso-8eA-hA and (±)-8eB-hB (diastereomers). The arylation of (S)-2-phenylbutanamide also gave the corresponding enantiomerically enriched compounds 10a-c (anti isomers). The stereochemistry of the products (±)-3a-l (major isomers), meso-8eA-hA (major isomers), (±)-8eB-hB (minor isomers) and enantiomerically enriched compounds 10a-c (major isomers) were assigned based on the X-ray structures of the major isomers 3b,c,e,l, 8eA, 10c and minor isomers 8eB and 8fB. The limitations and outcome of the stereocontrol in the Pd-catalyzed C-H arylation reactions involving aliphatic carboxamides are illustrated.
- Gopalakrishnan, Bojan,Babu, Srinivasarao Arulananda,Padmavathi, Rayavarapu
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p. 8333 - 8349
(2015/10/05)
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- Stereo- and Chemodivergent NHC-Promoted Functionalisation of Arylalkylketenes with Chloral
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Stereo- and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N-heterocyclic carbenes, giving selectively either β-lactones (up to 88:12 dr, up to 94% ee) or α-chloroesters (up to 94% ee). Either 2-arylsubstitution or an α-branched iPr alkyl substituent within the ketene favours the chlorination pathway, allowing chloral to be used as an electrophilic chlorinating reagent in asymmetric catalysis.
- Douglas, James J.,Churchill, Gwydion,Slawin, Alexandra M. Z.,Fox, David J.,Smith, Andrew D.
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supporting information
p. 16354 - 16358
(2015/11/09)
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- Pd(II)-catalyzed chelation-assisted cross dehydrogenative coupling between unactivated C(sp3)H bonds in aliphatic amides and benzylic CH bonds in toluene derivatives
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The chelation-assisted cross dehydrogenative coupling of C(sp3)H bonds is achieved by the Pd(II)-catalyzed reaction of aliphatic amides that contain a 5-chloro-8-aminoquinoline moiety as the directing group with toluene derivatives in the presence of heptafluoroisopropyl iodide. A variety of functional groups are tolerated.
- Kubo, Teruhiko,Aihara, Yoshinori,Chatani, Naoto
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supporting information
p. 1365 - 1367
(2015/11/24)
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- AZACYCLIC COMPOUNDS
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Compounds and methods are provided for the treatment of disease conditions in which modification of serotonergic receptor activity has a beneficial effect. In the method, an effective amount of a compound is adminstered to a patient in need of such treatment.
- -
-
Paragraph 0660
(2015/11/09)
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- Design and synthesis of tamoxifen derivatives as a selective estrogen receptor down-regulator
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We designed and synthesized an estrogen receptor (ER) down-regulator (5), which is a derivative of tamoxifen with a long alkyl side chain. Compound 5 effectively reduced ER protein levels in MCF-7 cells and had an antagonistic effect.
- Shoda, Takuji,Okuhira, Keiichiro,Kato, Masashi,Demizu, Yosuke,Inoue, Hideshi,Naito, Mikihiko,Kurihara, Masaaki
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- Synthesis, characterization and biological evaluation of novel diesters of 4,4'-dihydroxy azoxy benzene with long chain carboxylic acids
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Synthesis of novel symmetrical azoxy diesters have been prepared by the reaction of 4,4'-dihydroxyazoxy benzene with aliphatic acid halides of varying chain lengths. The synthesized compounds have been characterized by spectral and analytical data. These symmetrical azoxy diesters exhibit good antifungal activity against six fungal strains (Mucor species, Aspergillus niger, Aspergillus flavus, Alternaria solani, Fusarium solani and Aspergillus fumigatus) and antitumor activities while no significant antibacterial activity has been observed. These synthesized compounds are also potent free radical scavengers.
- Shehzadi, Sumaira,Siddiqi, Humaira Masood,Qasim, Malik Muhammed,Fawad, Musfirah,Manan, Abdul,Khan, Naeema,Saleem, Samreen,Bashir, Farah,Mirza, Bushra
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p. 462 - 472
(2014/08/05)
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- Palladium-catalyzed aryl C-H olefination with unactivated, aliphatic alkenes
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Palladium-catalyzed coupling between aryl halides and alkenes (Mizoroki-Heck reaction) is one of the most popular reactions for synthesizing complex organic molecules. The limited availability, problematic synthesis, and higher cost of aryl halide precursors (or their equivalents) have encouraged exploration of direct olefination of aryl carbon-hydrogen (C-H) bonds (Fujiwara-Moritani reaction). Despite significant progress, the restricted substrate scope, in particular noncompliance of unactivated aliphatic olefins, has discouraged the use of this greener alternative. Overcoming this serious limitation, we report here a palladium-catalyzed chelation-assisted ortho C-H bond olefination of phenylacetic acid derivatives with unactivated, aliphatic alkenes in good to excellent yields with high regio- and stereoselectivities. The versatility of this operationally simple method has been demonstrated through drug diversification and sequential C-H olefination for synthesizing divinylbenzene derivatives.
- Deb, Arghya,Bag, Sukdev,Kancherla, Rajesh,Maiti, Debabrata
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supporting information
p. 13602 - 13605
(2015/02/05)
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- Endoxifen is a new potent inhibitor of PKC: A potential therapeutic agent for bipolar disorder
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Protein kinase C (PKC) plays a major role in regulation of both pre and postsynaptic neurotransmission. Excessive activation of PKC results in symptoms related to bipolar disorder. Tamoxifen, a widely used breast cancer drug is known to inhibit PKC and demonstrate antimanic properties in human. We describe herein the synthesis of endoxifen, a tamoxifen active metabolite and compared its PKC inhibitory activity with that of tamoxifen. Endoxifen exhibited fourfold higher potency compared to tamoxifen.
- Ali, Shoukath M.,Ahmad, Ateeq,Shahabuddin, Syed,Ahmad, Moghis U.,Sheikh, Saifuddin,Ahmad, Imran
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body text
p. 2665 - 2667
(2010/07/05)
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- Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8- (trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury
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Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the α position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.
- Huang, Adrian,Moretto, Alessandro,Janz, Kristin,Lowe, Michael,Bedard, Patricia W.,Tam, Steve,Di, Li,Clerin, Valerie,Sushkova, Natalia,Tchernychev, Boris,Tsao, Desiree H. H.,Keith Jr., James C.,Shaw, Gray D.,Schaub, Robert G.,Wang, Qin,Kaila, Neelu
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experimental part
p. 6003 - 6017
(2010/11/19)
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- Oxindole synthesis by direct coupling of Csp2-H and C sp3-H centers
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(Chemical Equation Presented) An sp2/sp3 get-together: A novel and efficient method can be used to synthesize 3,3-disubstitued oxindoles by the direct intramolecular oxidative coupling of an aryl Csp2-H and a Csp3-H center (see scheme; DMF = N,N-dimethylformamide).
- Jia, Yi-Xia,Kuendig, E. Peter
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supporting information; experimental part
p. 1636 - 1639
(2009/06/30)
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- IBiox[(-)-menthyl]: A sterically demanding chiral NHC ligand
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(Figure Presented) An exceedingly sterically demanding, rigid, and chiral NHC ligand, IBiox[(-)-menthyl] (1), was prepared and structurally characterized. With a buried volume of 50percent, this ligand arguably represents one of the most sterically demanding monodentate ligands. The ability to use aryl chloride substrates in intramolecular palladium-catalyzed ,-arylations reveals its unique reactivity. Moreover, C2-symmetric 1 allows the highly enantioselective formation of oxindoles withup to 99percent ee.
- Wuertz, Sebastian,Lohre, Claudia,Froehlich, Roland,Bergander, Klaus,Glorius, Frank
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supporting information; experimental part
p. 8344 - 8345
(2009/10/24)
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- N-heterocyclic carbene-mediated enantioselective addition of phenols to unsymmetrical alkylarylketenes
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Chiral N-heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2-phenylphenol to unsymmetrical alkylarylketenes, delivering α-alkyl-α-arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee). Enantiodivergent stereochemical outcomes are observed using 2-phe-nylphenol and benzhydrol in the NHC-promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.
- Concellon, Carmen,Duguet, Nicolas,Smith, Andrew D.
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supporting information; experimental part
p. 3001 - 3009
(2010/03/26)
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- Methods and Compositions for Selectin Inhibition
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The present teachings relate to novel compounds of formula I: wherein the constituent variables are as defined herein. Compounds of the present teachings can act as antagonists of the mammalian adhesion proteins known as selecting. Methods for treating or preventing selectin-mediated disorders are provided, which include administration of these compounds in a therapeutically effective amount.
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Page/Page column 22
(2008/12/04)
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- USE OF 4-AMINO-PIPERIDINES FOR TREATING SLEEP DISORDERS
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Inverse agonists and antagonists of serotonin receptors are disclosed for use in treating sleep disorders such as insomnia, and specifically sleep maintenance insomnia. The compound increase slow wave sleep, decrease the number of awakenings after sleep onset, and decrease the time awake after sleep onset.
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Page/Page column 146-147
(2010/11/28)
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- Catalytic enantioselective construction of all-carbon quaternary stereocenters: Synthetic and mechanistic studies of the C-acylation of silyl ketene acetals
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With the aid of an appropriate chiral catalyst, acyclic silyl ketene acetals react with anhydrides to furnish 1,3-dicarbonyl compounds that bear all-carbon quaternary stereocenters in good ee and yield. Mechanistic studies provide strong support for a catalytic cycle that involves activation of both the electrophile (anhydride → acylpyridinium) and the nucleophile (silyl ketene acetal → enolate).
- Mermerian, Ara H.,Fu, Gregory C.
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p. 5604 - 5607
(2007/10/03)
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- Catalytic enantioselective synthesis of quaternary stereocenters via intermolecular C-acylation of silyl ketene acetals: Dual activation of the electrophile and the nucleophile
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A nucleophile-catalyzed asymmetric intermolecular C-acylation of silyl ketene acetals by anhydrides has been developed, furnishing quaternary stereocenters with high enantioselectivity. Mechanistic studies support the hypothesis that the reaction involves activation both of the silyl ketene acetal (generation of an enolate) and of the anhydride (formation of an acylpyridinium ion). Copyright
- Mermerian, Ara H.,Fu, Gregory C.
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p. 4050 - 4051
(2007/10/03)
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- Method for production of fluorine-containing aromatic compounds
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A method for the production of a fluorine-containing aromatic compound is provided which allows the relevant reaction to proceed in a standard reaction vessel such as, for example, a glass vessel at room temperature under an ambient pressure without requiring provision of such special devices as have been necessary heretofore or adoption of harsh reaction conditions. This method comprises causing an aromatic compound (A) having a cyclic skeletal part of 6 to 16 carbon atoms containing a plurality of -C(=O)X groups, wherein X stands for a hydrogen atom, a halogen atom, or an alkyl group of 1 to 10 carbon atoms, and having the remaining hydrogen atoms unsubstituted or partly or wholly substituted with at least one species of halogen atom to react with a compound (B) represented by the formula: wherein R1 and R2 independently stand for an alkyl group of 1 to 6 carbon atoms or a phenyl group.
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- Enantiospecific synthesis of 4-(4'-methoxyphenyl)-hexan-3-one as precursor for optically active (pS) or (pR) isomer of (Z) or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene
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We describe herein an original method for the preparation of enantiomerically pure (Z)- or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene possessing a p(S) or p(R) plane of chirality. The key step of the synthesis lies in obtaining enantiomerically pure (R) or (S) 4-(4'-methoxyphenyl)-hexan-3-one whose reaction with the lithiated N,N-dimethylaminomethylferrocene leads to two enantiomerically pure amino-alcohol diastereomers (pS,3S,4R) and (pR,3S,4R), or (pS,3R,4S) and (pR,3R,4S) respectively. Subsequent dehydration yields a mixture of three olefins, namely, two trisubstituted olefins and either the (Z)- or (E)-tetrasubstituted olefin with respect to the starting amino-alcohol diastereomer. Additionally we obtained the enantiomerically pure (R)- and (S)-4-phenyl-hexan-3-one and the corresponding diastereomeric amino-alcohols.
- Malezieux, Bernard,Gruselle, Michel,Troitskaya, Ludmila,Sokolov, Viatcheslav
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p. 259 - 269
(2007/10/03)
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- N-acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents
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The present invention is directed to compounds useful for the regulation of cholesterol of Formula I, methods for using them and pharmaceutical compositions thereof, STR1 wherein X and Y are oxygen, sulfur, or (CR'R")n wherein n is 1 to 4; R is hydrogen, alkyl, or benzyl; R1 and R2 are phenyl, substituted phenyl, naphthyl, substituted naphthyl, an aralkyl group, an alkyl chain, adamantyl, or a cycloalkyl group.
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- Deracemization of α-substituted arylacetic acids
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Reaction of rac-α-substituted arylacetyl chlorides with (R)- and (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone under standard esterification conditions, gave esters (3R,αR)- and (3S,αS)-3, respectively, with a diastereoselectivity which diminishes on increasing the steric effect of the α-substituent. Controlled acidic hydrolysis of esters 3 afforded the corresponding acids 4 with minimal racemization. Boron tribromide demethylation of (R)- and (S)-4d gave without racemization the hydroxyacids (R)- and (S)-4e, known precursors of (R)- and (S)-iodoalphionic acid.
- Camps, Pelayo,Gimenez, Silvia
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p. 1227 - 1234
(2007/10/03)
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- ortho-Directed electrophilic boronation of a benzyl ketone: the preparation, X-ray crystal structure, and some reactions of 4-ethyl-1-hydroxy-3-(4-hydroxyphenyl)-2-oxa-1-boranaphthalene
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4-Ethyl-1-hydroxy-3-(4-hydroxyphenyl)-2-oxa-1-boranaphthalene (4) is formed in 78percent yield from the reaction of 1-(4-metho-xyphenyl)-2-phenylbutan-1-one with an of excess boron tribromide in dichloromethane followed by treatment with water.Reaction of 4 with iodine in aqueous sodium hydroxide gives a second oxaboracycle, 3-ethyl-1-hydroxy-3-(4-hydroxybenzoyl)-2,1-benzoxaborolane (5).The X-ray crystal structure determinations of both boron heterocycles are reported.Other new compounds reported are 1-(4-hydroxyphenyl)-2-(1-hydroxyphenyl)-butan-1-one (6), formed by reaction of 4 with alkaline hydrogen peroxide, and 1-(4-hydroxyphenyl)-2-(2-biphenyl)-butan-1-one (8), formed by coupling of 4 with bromobenzene in the presence of Pd(PPh3)4.
- Arcus, Vickery L.,Main, Lindsay,Nicholson, Brian K.
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p. 139 - 148
(2007/10/02)
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- OXIDANT SENSITIVE AND INSENSITIVE AROMATIC ESTERS AS INHIBITORS OF HUMAN NEUTROPHIL ELASTASE
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2-Phenylalkanoate esters which are useful as inhibitors of human leukocyte elastase.
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- Thermal Decomposition of 2-Amino-3-aziridino-1,4-naphthoquinones (1,2)
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The course of the thermal decomposition of various 2-amino-3-substituted aziridino-1,4-naphthoquinones (Ia-g) was investigated.In all the cases, the thermal decomposition gave variable amounts of 2,3-diamino-1,4-naphthoquinone (II) and of substituted 1,2,3,4,5,10-hexahydrobenzoquinoxaline-5,10-diones (IIIa-g) with complete stereospecifity.The decomposition of the aziridines Ib,f also gave significative amounts of 2-amino-3-allylamino-1,4-naphthoquinones (IVb,f).In the case of 2-amino-3-(2'-phenyl-3'-ethylaziridino)-1,4-naphthoquinone (Ig), the formation of trans-1-phenyl-1-butene (V), 2-(1-phenylpropyl)-1H-napthoimidazole-4,9-dione (VI), 2-phenyl-3-ethyl-3,4,5,10-tetrahydrobenzoquinoxaline-5,10-dione (VII), 2-phenyl-3-ethyl-5,10-dihydrobenzoquinoxaline-5,10-dione (VIII), and a mixture of cis- and trans-4H-2,3,5,6-tetrahydro-2-phenyl-3-ethyl-5-iminonaphthooxazin-6-one (IX) also occured.Hypotheses concerning the mechanism and the steric course of this reaction are given.The reaction is a general method for the stereospecific synthesis of 2,3-disubstituted 1,2,3,4,5,10-hexahydrobenzoquinoxalines.
- Antonini, Ippolito,Claudi, Francesco,Cristalli, Gloria,Grifantini, Mario,Martelli, Sante
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p. 399 - 404
(2007/10/02)
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- Soft drugs: III. A new class of anticholinergic agents
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A new class of antimuscarinic drugs was designed and synthesized. The compounds are 'soft' quaternary ammonium esters in which there is only one carbon atom separating the ester oxygen and the quaternary head. The compounds are potent anticholinergics when derived from hindered 'umbrella' acids and cholinergics when derivatives of simple aliphatic acids. The more potent anticholinergics have up to 10 times higher acetylcholine antagonist activity than atropine, but they have a much shorter duration of action. The compounds cleave hydrolytically with simultaneous destruction of the quaternary head. The compounds are promising as selective, local agents, particularly as inhibitors of eccrine sweating.
- Bodor,Woods,Raper,et al.
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p. 474 - 480
(2007/10/02)
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