- Phosphine-Catalyzed Intramolecular Vinylogous Aldol Reaction of α-Substituted Enones
-
We demonstrate the first phosphine-catalyzed intramolecular vinylogous aldol reaction (IVAR) of α-substituted enones. This strategy provides access to various pentannulated (hetero)arenes and dibenzocycloheptanones incorporated with two contiguous stereocenters, one of which is an all-carbon quaternary center. The scope of this work is further broadened through elaborations of the IVAR adducts to (i) benzannulated nine-membered carbocyclic systems, (ii) interesting classes of 1,3-dienes, 1,3,5-trienes, and 1-yn-3,5-dienes, and (iii) the analogs of echinolactone D and russujaponol F.
- Mondal, Atanu,Satpathi, Bishnupada,Ramasastry
-
supporting information
p. 256 - 261
(2022/01/04)
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- Cobalt-Catalyzed Chemoselective Transfer Hydrogenative Cyclization Cascade of Enone-Tethered Aldehydes
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The ligand-free Co-catalyzed chemoselective reductive cyclization cascade of enone-tethered aldehydes with i-PrOH as the environmentally benign hydrogen surrogate is developed by this study. Mechanistic studies disclosed that such a protocol is initiated
- Ma, Shuang-Shuang,Jiang, Biao-Ling,Yu, Zheng-Kun,Zhang, Suo-Jiang,Xu, Bao-Hua
-
supporting information
p. 3873 - 3878
(2021/05/26)
-
- Copper-Catalyzed Tandem Cross-Coupling and Alkynylogous Aldol Reaction: Access to Chiral Exocyclic α-Allenols
-
An enantioselective copper-catalyzed tandem cross-coupling/alkynylogous aldol reaction has been developed. The tetrasubstituted allenoates containing both central and axial chirality have been obtained in moderate to good yields and excellent enantio-and
- Xu, Guangyang,Wang, Zhen,Shao, Ying,Sun, Jiangtao
-
supporting information
p. 5175 - 5179
(2021/07/19)
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- Palladium-Catalzyed Atroposelective 16-Membered Macrocyclization: Total Synthesis of Isoplagiochin D?
-
Isoplagiochin D is a ring-strained macrocyclic bisbibenzylis, which showed stable axial chirality in one biaryl structure, and semistable axial chirality in the other biaryl moiety. We reported here an unprecedented example for the catalytically asymmetri
- Xi, Junwei,Gu, Zhenhua
-
supporting information
p. 1081 - 1085
(2020/07/06)
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- Chiral phosphine nitrogen phosphine ligand and chiral metal organic coordination complex and application
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The invention discloses a chiral phosphine nitrogen phosphine ligand and chiral metal organic coordination complex and application. The chiral tridentate phosphine nitrogen phosphine ligand is shown as a formula (I), and the chiral metal organic coordination complex is shown as a formula (II), wherein the chiral metal organic coordination complex shown as the formula (II) is used as a homogeneouscatalyst to be applied to preparation of phenylalanine derivatives with high optical activity. The novel chiral nitrogen-phosphine ligand synthesized by taking cheap amino acid as a chiral source is applied to asymmetric hydrogenation reaction, and a chiral product with relatively high yield can be obtained with relatively low catalytic dosage, relatively short reaction time and relatively mild reaction conditions.
- -
-
Paragraph 0075-0077
(2020/07/02)
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- Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals
-
The metalloradical activation of o-aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [CoII(TPP)]-catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8-membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8-membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis-allylic/benzallylic C?H bond to the carbene radical, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8π-cyclization, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.
- Lankelma, Marianne,Zhou, Minghui,de Bruin, Bas,van der Vlugt, Jarl Ivar
-
supporting information
p. 11073 - 11079
(2020/04/29)
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- Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as the RXRα Activator to Inhibit Colon Cancer
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We reported recently that berberine (Ber), a traditional oriental medicine to treat gastroenteritis, binds and activates retinoid X receptor α (RXRα) for suppressing the growth of colon cancer cells. Here, we extended our studies based on the binding mode of Ber with RXRα by design, synthesis, and biological evaluation of a focused library of 15 novel Ber analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than Ber, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing the Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved Ber's tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of Ber-derived RXRα activators as novel effective antineoplastic agents for colon cancer.
- Xu, Beibei,Jiang, Xunjin,Xiong, Jing,Lan, Jun,Tian, Yuan,Zhong, Linhai,Wang, Xinquan,Xu, Ning,Cao, Hanwei,Zhang, Wenqing,Zhang, Hao,Hong, Xiaoting,Zhan, Yan-Yan,Zhang, Yandong,Hu, Tianhui
-
p. 5841 - 5855
(2020/07/03)
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- Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
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Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
- Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
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p. 5852 - 5869
(2018/11/10)
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- Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine
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One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.
- D'Hollander, Agathe C.A.,Westwood, Nicholas J.
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supporting information
p. 224 - 239
(2017/12/08)
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- Catalytic Dibenzocyclooctene Synthesis via Cobalt(III)–Carbene Radical and ortho-Quinodimethane Intermediates
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The metalloradical activation of ortho-benzallylaryl N-tosyl hydrazones with [Co(TPP)] (TPP=tetraphenylporphyrin) as the catalyst enabled the controlled exploitation of the single-electron reactivity of the redox non-innocent carbene intermediate. This method offers a novel route to prepare eight-membered rings, using base metal catalysis to construct a series of unique dibenzocyclooctenes through selective Ccarbene?Caryl cyclization. The desired eight-membered-ring products were obtained in good to excellent yields. A large variety of aromatic substituents are tolerated. The proposed reaction mechanism involves intramolecular hydrogen atom transfer (HAT) to CoIII–carbene radical intermediates followed by dissociation of an ortho-quinodimethane that undergoes 8π cyclization. The mechanism is supported by DFT calculations, and the presence of radical-type intermediates was confirmed by trapping experiments.
- te Grotenhuis, Colet,van den Heuvel, Naudin,van der Vlugt, Jarl Ivar,de Bruin, Bas
-
supporting information
p. 140 - 145
(2017/12/13)
-
- Asymmetric Transfer Hydrogenation of (Hetero)arylketones with Tethered Rh(III)-N-(p-Tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine Complexes: Scope and Limitations
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A series of new tethered Rh(III)/Cp? complexes containing the N-(p-tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine ligand have been prepared, characterized, and evaluated in the asymmetric transfer hydrogenation (ATH) of a wide range of (hetero)aryl ketones. The reaction was performed under mild conditions with the formic acid/triethylamine (5:2) system as the hydrogen source and provided enantiomerically enriched alcohols with good yields and high to excellent enantioselectivities. Although the nature of the substituents on the phenyl tethering ring did not alter the stereochemical outcome of the reaction, complexes bearing electron-donating groups exhibited a higher catalytic activity than those having electron-withdrawing groups. A scale-up of the ATH of 4-chromanone to the gram scale quantitatively delivered the reduced product with excellent enantioselectivity, demonstrating the potential usefulness of these new complexes.
- Zheng, Long-Sheng,Llopis, Quentin,Echeverria, Pierre-Georges,Férard, Charlène,Guillamot, Gérard,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie
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p. 5607 - 5615
(2017/06/07)
-
- Enantioselective N-Heterocyclic Carbene Catalysis by the Umpolung of α,β-Unsaturated Ketones
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N-Heterocyclic carbene-catalyzed formation of β-anionic intermediates from enones has been employed in the enantioselective synthesis of 2-aryl propionates. The reaction was achievable using a homochiral 4-MeOC6H4 morpholinone cataly
- Nakano, Yuji,Lupton, David W.
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p. 3135 - 3139
(2016/03/12)
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- (Biphenyl-2-alkyne) derivatives as common precursors for the synthesis of 9-iodo-10-organochalcogen-phenanthrenes and 9-organochalcogen-phenanthrenes
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In this paper, we report our results on the cyclization of (biphenyl-2-alkyne) derivatives to give two different types of phenanthrene derivatives, 9-iodo-10-organochalcogen-phenanthrenes and 9-organochalcogen-phenanthrenes. The strategy for the synthesis was based on the use of electrophilic cyclization for the preparation of 9-iodo-10-organochalcogen-phenanthrenes and iron(iii) chloride/diorganyl diselenide-mediated intramolecular cyclization to prepare 9-organochalcogen-phenanthrenes. The effects of solvent, temperature, reaction time and stoichiometry on the efficiency of cyclization reactions were investigated. The standard reaction conditions were compatible with many functional groups in the substrates, such as methyl, chlorine, fluorine and methoxyl. This protocol was efficient for diorganyl diselenides and disulfides but ineffective for diorganyl ditellurides. The resulting phenanthrenes were further functionalized through Sonogashira reactions followed by the electrophilic cyclization reaction to give the selenophene-fused aromatic compounds.
- Grimaldi, Tamiris B.,Lutz, Guilherme,Back, Davi F.,Zeni, Gilson
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p. 10415 - 10426
(2016/11/18)
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- Synthesis, characterization and use of a new tethered Rh(III) complex in asymmetric transfer hydrogenation of ketones
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A new Rh(III) complex containing the TsDPEN ligand and an η6-arene connected through a carbon tether is reported. The asymmetric transfer hydrogenation of a series of ketones catalyzed by this complex using the formic acid/triethylamine system provided the corresponding alcohols with complete conversions and a high level of enantioselectivity.
- Echeverria, Pierre-Georges,Férard, Charlène,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie
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-
- Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
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Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities.
- Parrino, Barbara,Carbone, Anna,Ciancimino, Cristina,Spanò, Virginia,Montalbano, Alessandra,Barraja, Paola,Cirrincione, Girolamo,Diana, Patrizia,Sissi, Claudia,Palumbo, Manlio,Pinato, Odra,Pennati, Marzia,Beretta, Giovanni,Folini, Marco,Matyus, Peter,Balogh, Balázs,Zaffaroni, Nadia
-
p. 149 - 162
(2015/03/18)
-
- Synthesis of Diverse 6-Oxa-allocolchicinoids by a Suzuki-Miyaura Coupling, Acid-Catalyzed Intramolecular Transacetalization Strategy
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The synthesis of allocolchicine analogues is of importance as these compounds have been found to possess promising anticancer activity by affecting tubulin polymerization. In this paper, the synthesis of 28 novel substituted 6-oxa-allocolchicinoids is rep
- Yadav, Dharmendra B.,Taleli, Lebusetsa,Van Der Westhuyzen, Alet E.,Fernandes, Manuel A.,Dragoun, Maxim,Prokop, Aram,Schmalz, Hans-Günther,De Koning, Charles B.,Van Otterlo, Willem A. L.
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p. 5167 - 5182
(2015/08/18)
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- CRYSTALLINE FORM OF 6-[(4S)-2-METHYL-4-(2-NAPHTHYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-YL]PYRIDAZIN-3-AMINE
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The present disclosure generally relates to a crystalline form of 6-[(4S)-2-methyl-4-(naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine. The present disclosure also generally relates to pharmaceutical compositions comprising the crystalline form, as well of methods of using a crystalline form in the treatment of depression and other conditions and methods for obtaining such crystalline form.
- -
-
Paragraph 0072; 0131; 0132
(2014/09/30)
-
- Synthesis of 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides via ortho lithiation of protected benzaldehyde derivatives
-
Variously substituted 2-phenyl-1,3-dioxolanes and 2-(2-bromophenyl)-1,3- dioxolanes, prepared from the corresponding benzaldehydes, were lithiated ortho to the acetal group. Reaction of the lithio derivatives with sulfur dioxide led to the lithium sulfinate salts, which gave, upon oxidative chlorination with sulfuryl chloride, the corresponding benzenesulfonyl chlorides. Then, depending on the aromatic substitution pattern of the molecule, several protocols were elaborated for the functional group transformations leading to the target compounds. Ring closure was performed with hydrazine hydrate or acetylhydrazine, in the latter case with one-pot removal of the acetyl group. The 4-unsubstituted 2H-1,2,3-benzothiadiazine 1,1-dioxides thus obtained are potential drug candidates based on their structural similarity to biologically active phthalazinones.
- Porcs-Makkay, Márta,Lukács, Gyula,Pandur, Angéla,Simig, Gyula,Volk, Balázs
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p. 286 - 293
(2014/01/06)
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- NHC-catalyzed oxidative cyclization reaction for the synthesis of 3-substituted phthalides
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An efficient NHC-catalyzed domino oxidation/oxa-Michael addition reaction of 2-alkenylbenzaldehydes has been developed to afford 3-substituted phthalides bearing a C3-stereogenic center with a broad substrate scope and wide functional group tolerance. The preliminary results of the asymmetric process have been provided as well. the Partner Organisations 2014.
- Youn, So Won,Song, Hyoung Sub,Park, Jong Hyub
-
supporting information
p. 2388 - 2393
(2014/04/03)
-
- Organocatalytic, Enantioselective, intramolecular oxa-michael reaction of alkoxyboronate: A new strategy for enantioenriched 1-substituted 1,3-Dihydroisobenzofurans
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An unprecedented strategy for the synthesis of enantioenriched 1-substituted 1,3-dihydroisobenzofurans via an enantioselective oxa-Michael reaction of o-alkoxyboronate containing chalcone (II) has been accomplished employing cinchona alkaloid based squara
- Ravindra, Barnala,Das, Braja Gopal,Ghorai, Prasanta
-
supporting information
p. 5580 - 5583
(2015/02/19)
-
- One-pot syntheses of isoquinolin-3-ones and benzo-1,4-diazepin-2,5-diones utilizing Ugi-4CR post-transformation strategy
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One-pot and efficient syntheses of structurally diverse isoquinolin-3-ones and isoquinolin-3-one-based benzo-1,4-diazepin-2,5-diones have been developed. The notable features of the process include the Ugi condensation of monomasked phthalaldehydes with a
- Che, Chao,Li, Song,Yu, Zhixiong,Li, Fangfang,Xin, Shengchang,Zhou, Liyan,Lin, Shuo,Yang, Zhen
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supporting information
p. 202 - 207
(2013/05/09)
-
- An efficient route to polysubstituted tetrahydronaphthols: Silver-catalyzed [4+2] cyclization of 2-alkylbenzaldehydes and alkenes
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Silver bullet: A methodology for stereoselective synthesis of polysubstituted tetrahydronaphthols catalyzed by [Ag+]/NPO has been developed. The reactions proceeded through an unprecedented [4+2] cyclization of 2-(2-formylphenyl)ethanone and an alkene, in both inter- and intramolecular fashion. NPO=pyridine N-oxide. Copyright
- Zhu, Shifa,Liang, Renxiao,Jiang, Huanfeng,Wu, Wanqing
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supporting information
p. 10861 - 10865
(2013/01/15)
-
- Total synthesis of plagiochin D by an intramolecular SNAr reaction
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The total synthesis of plagiochin D, a macrocyclic bis(bibenzyl) compound isolated from the liverwort plagiochila acanthophylla, has been accomplished. Closure of the key 16-membered ring, which contained biphenyl ether and biaryl units, was achieved in good yield by an intramolecular SNAr reaction. The Suzuki and Wittig protocols proved to be powerful tools for the construction of a linear precursor that was crucial for ring cyclization. Copyright
- Cortes Morales, Julio Cesar,Guillen Torres, Alejandro,Gonzalez-Zamora, Eduardo
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experimental part
p. 3165 - 3170
(2011/06/28)
-
- NHC-catalyzed spiro bis-indane formation via domino stetter - Aldol - Michael and stetter - Aldol - Aldol reactions
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Two novel domino NHC-catalyzed spirocyclizations are described herein, enabling the rapid construction of three new carbon - carbon bonds and a quaternary center with high diastereoselectivity. A variety of spiro bis-indane structures are assembled in a single step from simple o-phthaldialdehyde derivatives.
- Sanchez-Larios, Eduardo,Holmes, Janice M.,Daschner, Crystal L.,Gravel, Michel
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supporting information; experimental part
p. 5772 - 5775
(2011/03/22)
-
- CRYSTALLINE FORM OF 6-[(4S)-2-METHYL-4-(2-NAPHTHYL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-YL]PYRIDAZIN-3-AMINE
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The present disclosure generally relates to a crystalline form of 6-[(4S)-2-methyl-4-(naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine. The present disclosure also generally relates to pharmaceutical compositions comprising the crystalline form, as well of methods of using a crystalline form in the treatment of depression and other conditions and methods for obtaining such crystalline form.
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Page/Page column 22; 43
(2009/12/28)
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- Metal-catalyzed cycloisomerization of enyne functionalities via a 1,3-alkylidene migration
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We report a new metal-catalyzed 6-endo-dig cyclization of cis-4,6-dien-1-yn-3-ols, which produces substituted benzene and naphthalene derivatives with structural reorganization. In this process, we observe a 1,3-alkylidene migration via cleavage of the olefin double bond of the starting substrates. The ease and reliability of this cyclization are manifested by its compatibility with a wide array of diverse substrates and several π-alkyne activators, including PtCl2, Zn(OTf)2, AuCl, and AuCl3. Copyright
- Lin, Ming-Yuan,Das, Arindam,Liu, Rai-Shung
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p. 9340 - 9341
(2007/10/03)
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- Synthesis of a highly soluble superstructured phenanthroline strapped porphyrin
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A highly soluble phenanthroline strapped porphyrin is prepared on multigram scale by appropriate functionalization with C12 chains a posteriori to the efficient cyclization of the tetrapyrrolic macrocycle. A highly soluble phenanthroline strapp
- Koepf, Matthieu,Melin, Frédéric,Jaillard, Jér?me,Weiss, Jean
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p. 139 - 142
(2007/10/03)
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- 3-ARYLOXY/ THIO-2, 3-SUBSTITUTED PROPANAMINES AND THEIR USE IN INHIBITING SEROTONIN AND NOREPINEPHRINE REUPTAKE
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There is provided a compound of formula (I) wherein A is selected from -O- and -S-; X is selected from phenyl optionally substituted with up to 5 substituents each independently selected from halo, C1-C4 alkyl and C1-C4 alkoxy, thienyl optionally substituted with up to 3 substituents each independently selected from halo and C1-C4 alkyl, and C2-C8 alkyl, C2-C8 alkenyl, C3-C8 cycloalkyl and C4-C8 cycloalkylalkyl, each of which may be optionally substituted with up to 3 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, -CF3, -CN and -CONH2; Y is selected from phenyl, naphthyl, dihydrobenzothienyl, benzothiazolyl, benzoisothiazolyl, quinolyl, isoquinolyl, naphthyridyl, thienopyridyl, indanyl, 1,3-benzodioxolyl, benzothienyl, indolyl and benzofuranyl, each of which may be optionally substituted with up to 4 or, where possible, up to 5 substituents each independently selected from halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkyl-S(O)n- where n is 0, 1 or 2, nitro, acetyl, -CF3, -SCF3 and cyano; and when Y is indolyl it may be substituted or further substituted by an N-substituent selected from C1-C4 alkyl; Z is selected from OR3 or F, wherein R3 is selected from H, C1-C6 alkyl and phenyl C1-C6 alkyl; R1 and R2 are each independently H or C1-C4 alkyl; and pharmaceutically acceptable salts thereofwith the proviso that when Y is optionally substituted phenyl or optionally substituted 1,3-benzodioxolyl and Z is OR3 and X is optionally substituted phenyl then A is -S-.
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Page 30 - 31
(2010/02/07)
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- Rhodium-catalyzed tandem cyclization: Formation of 1H-indenes and 1-alkylideneindans from arylboronate esters in aqueous media
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Arylboronate esters bearing a pendant Michael-type acceptor olefin or acetylene linkage undergo transmetalation with a rhodium-based catalytic complex to generate a functionalized organorhodium intermediate which can cyclize onto nonterminal acetylenes in
- Lautens, Mark,Marquardt, Tzvetelina
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p. 4607 - 4614
(2007/10/03)
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- Substituted phenyl compounds
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Compounds of formula (I) are described wherein R1is hydrogen, -(lower alkyl)q(CO2R6or OH), —CN, —C(R7)═NOR8, NO2, —O(lower alkyl)R9, —C≡C—R10, —CR11═C(R12)(R13), —C(═O)CH2C(═O)CO2H, —CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4and R5are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.
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- Synthesis of trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,2-b]-[1]benzothiophene, A potentially carcinogenic metabolite of sulfur heterocycle phenanthro[3,2-b][1]benzothiophene
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The present study describes the synthesis of trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,2-b][1]benzothiophene (3), which is a potential proximate carcinogen of the environmentally occurring potent carcinogen phenanthro-[3,2-b][1]benzothiophene (1). Three approaches were investigated for the synthesis of 3. In the first approach, the diarylalkene 9, which was prepared by the Wittig reaction of ylide 7 and aldehyde 8, was subjected to an oxidative photocyclization reaction to produce a mixture of compounds from which 5, a synthetic precursor to 3, was obtained only in trace amounts. The major cyclized product was 10. The second approach entailed the Suzuki cross-coupling reaction of 2-(dihydroxyboryl)-5-methoxybenzaldehyde (12) with 3-bromodibenzothiophene (11) to produce 13 in 92% yield. The aldehyde function of 13 was elongated with trimethylsulfonium iodide in the presence of KOH to generate the ethylene oxide 14, which, after methanesulfonic acid treatment, produced a 1 : 1 mixture of 3-methoxyphenanthro[3,2-b][1]benzothiophene (6) and 3-methoxyphenanthro[1,2-b][1]benzothiophene (15). Only the undesired compound 15 could be isolated in pure form by extracting the mixture with hot ethanol, leaving behind a 7 : 3 mixture of 6 and 15. In the third approach, the Wittig reaction of 7 with 2-bromo-5-methoxybenzaldehyde (16) produced 17 predominantly as the Z-isomer in quantitative yield. Cyclodehydrobromination of 17 with KOH-quinoline at elevated temperature produced a mixture from which 6 and 3-methoxyphenanthro[3,4-b][1]benzothiophene (18) were easily separated by column chromatography in 23 and 51% yields, respectively. The intermediate 6 was conveniently processed to 3 following the reaction sequence: methoxy phenol→o-quinone→dihydrodiol. A relatively polar dihydrodiol obtained by similar processing of the mixture of 6 and 15 was identified as 3.
- Kumar, Subodh
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p. 1018 - 1023
(2007/10/03)
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- A convenient access to benzo-substituted phthalazines as potential precursors to DNA intercalators
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2-Nitro-5-methoxybenzaldehyde is converted to amines 2 and 7 via two alternative routes. Upon diazotisation and Sandmeyer reaction, halides 4 and 9 are formed, which, through lithiation and formylation lead to the o-phthalaldehyde. Further cyclisation with hydrazine gives the 5-methoxy-substituted phthalazine.
- Tsoungas, Petros G,Searcey, Mark
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p. 6589 - 6592
(2007/10/03)
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- AMINO ACID DERIVATIVES AND THEIR USE AS THROMBIN INHIBITORS
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There is provided compounds of formula I, wherein R 1, R 2, R 3, R x, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required as in thrombosis or as anticoagulants.
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- Selective endothelin a receptor antagonists. 4. Discovery and structure- activity relationships of stilbene acid and alcohol derivatives
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This publication describes the synthesis and optimization of a novel series of stilbene endothelin antagonists. Analysis of the SAR established for previous papers in this series prompted the design and synthesis of (Z)- 4-phenyl-5-(3-benzyloxyphenyl)pent-4-enoic acid 3 which was found to be a moderately active inhibitor of the binding of [125I]ET-1 to ET(A) receptors with an IC50 of 6 μM. More interestingly, the intermediate compound (E)-2-phenyl-3-(3-benzyloxyphenyl)propenoic acid 5 was equiactive with 3. Optimization of 5 resulted in the preparation of (E)2-phenyl-3-(2- cyano-5-(thien-3-ylmethoxy))phenylpropenoic acid 18 (RPR111723) which had an IC50 in the binding assay of 80 nM on the ET(A) receptor and a pK(B) of 6.5 in the functional assay, measured on rat aortic strips. Reduction of the acid group of 5 gave the first nonacidic ET(A) antagonist in our series, (E)-2- phenyl-3-(3-benzyloxyphenoxy)prop2-enol 6 with an IC50 of 20 μM. Optimization of 6 resulted in the preparation of 2-(2-methylphenyl)-3-(2- cyano-5-(thien3-ylmethyl)phenyl)prop-2-enol 33 with an IC50 of 300 nM on the ET(A) receptor.
- Astles, Peter C.,Brown, Thomas J.,Halley, Frank,Handscombe, Caroline M.,Harris, Neil V.,McCarthy, Clive,McLay, Iain M.,Lockey, Peter,Majid, Tahir,Porter, Barry,Roach, Alan G.,Smith, Christopher,Walsh, Roger
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p. 2745 - 2753
(2007/10/03)
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- Facile Intramolecular Tosylhydrazone-Mediated Cyclopropanation Reactions of 4-(2-Formylphenyl)-1,4-dihydropyridines
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Hantzsch-type 4-(2-formylphenyl)-1,4-dihydropyridine derivatives 4-7 undergo facile intramolecular tosylhydrazone-mediated cyclopropanation reactions to afford the highly constrained analogues 16-19, respectively.Prior formation of the conjugate anions of
- Remy, David C.,King, Stella W.,Cochran, David,Springer, James P.,Hirshfield, Jordon
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p. 4120 - 4125
(2007/10/02)
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