- Amido compounds as RORγt modulators and uses thereof
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Amido compounds are disclosed that have a formula represented by the following: and wherein Cy1, Cy2, n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.
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Page/Page column 72
(2017/09/30)
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- Microwave-Assisted Synthesis of Phenylpropanoids and Coumarins: Total Synthesis of Osthol
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Herein we describe a one-pot microwave-assisted method for the synthesis of cinnamic acid and coumarin derivatives. The synthesis begins with an aldehyde synthon, and the chosen reaction conditions determine whether a cinnamic acid or coumarin derivative is formed. A regioselective Claisen rearrangement was also efficiently incorporated into the synthetic sequence to further increase the complexity of the product. Notably, this approach provides high product yields and selectivities without the need of a phenol protecting group.
- Konrádová, Daniela,Kozubíková, Hana,Dole?al, Karel,Pospí?il, Ji?í
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supporting information
p. 5204 - 5213
(2017/09/29)
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- Rh-Catalyzed Synthesis of Coumarin Derivatives from Phenolic Acetates and Acrylates via C-H Bond Activation
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An efficient annulation strategy involving the reaction of phenolic acetates with acrylates in the presence of [Rh2(OAc)4] as catalyst and formic acid as reducing agent, leading to the high yield synthesis of coumarin derivatives, has been developed. The addition of NaOAc as a base increased the yield of the products. The reaction is quite successful for both electron-rich as well as electron-deficient phenolic acetates, affording coumarins with excellent regioselectivity, and proceeds via C-H bond activation proven by deuterium incorporation studies.
- Gadakh, Sunita K.,Dey, Soumen,Sudalai, Arumugam
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p. 11544 - 11550
(2015/12/04)
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- Reduction of substituted phenyl 2-chloroacetates at silver cathodes: Electrosynthesis of coumarins
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To explore the electrosynthesis of coumarins, cyclic voltammetry and controlled-potential (bulk) electrolysis have been employed to investigate the reduction of the carbon-chlorine bond of five substituted phenyl 2-chloroacetates at silver cathodes in dimethylformamide (DMF) containing 0.10 M tetra-n-butylammonium tetrafluoroborate (TBABF4) as supporting electrolyte; the five substrates are 2-formylphenyl 2-chloroacetate (1a), 2-acetylphenyl 2-chloroacetate (2a), methyl 2-(2-chloroacetoxy)benzoate (3a), 2-formyl-5-methoxyphenyl 2-chloroacetate (4a), and 2-formyl-3,5-dimethoxyphenyl 2-chloroacetate (5a). We have examined (a) the effects of substituents on the benzene ring of the substrate as well as the nature of the aryl carbonyl moiety on the formation of the coumarin product and (b) the effect of solvent - namely, DMF, acetonitrile (CH3CN), benzonitrile (PhCN), and propylene carbonate (PC) - and substrate concentration on the yield of the coumarin. It was found that the most unsubstituted substrate (1a) afforded the highest yield (41%) of the desired coumarin in a DMF-TBABF4 medium. A mechanistic scheme is proposed to account for the formation of the coumarin. Furthermore, the only other products seen in these reductions are 2-substituted phenols, which are precursors for synthesis of the various substrates.
- Pasciak, Erick M.,Peters, Dennis G.
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p. G98 - G102
(2015/04/14)
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- AMIDO COMPOUNDS AS RORGAMMATMODULATORS AND USES THEREOF
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Amido compounds are disclosed that have a formula represented by the following: 1 and wherein Cy1, Cy2, n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graftversus-host disease
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Paragraph 00366
(2013/03/26)
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- A catalyst-free one-pot construction of skeletons of 5-methoxyseselin and alloxanthoxyletin in water
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In refluxing water and without an additional catalyst, electron-rich phenols could react with alkynoic acids or alkynoates to provide coumarin structures. The skeletons of two natural pyranocoumarins, 5-methoxyseselin and alloxanthoxyletin, could be constructed (total yield up to 76%) in an aqueous multicomponent reaction in which isoprenyl acetate, propiolic acid, and phloroglucinol were simply mixed and refluxed in water.
- Cao, Jin-Li,Shen, Su-Li,Yang, Peng,Qu, Jin
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supporting information
p. 3856 - 3859
(2013/09/02)
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- Cascade synthesis of 3-alkenylcoumarins by palladium-catalyzed reaction of phenols and ethyl propiolate
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A highly effective cascade process giving 3-alkenylcoumarins is furnished by a series of reactions involving palladaarylation of ethyl propiolate with phenols, intramolecular transesterification to 3-coumarylpalladium species, its alkyne insertion, and protonation. [Pd(OAc)2(dppe)] is an effective catalyst for the synthesis of 3-alkenylcoumarins from phenols and ethyl propiolate.
- Kitamura, Tsugio,Tatemoto, Kotaro,Sakai, Mariko,Oyamada, Juzo
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supporting information; experimental part
p. 705 - 707
(2012/09/22)
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- Synthesis of coumarins and neoflavones through zinc chloride catalyzed hydroarylation of acetylenic esters with phenols
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Acetylenic esters react with oxygenated phenols under solvent-free conditions in the presence of only 5 mol% of zinc chloride as a catalyst to give coumarins and neoflavones in reasonable-to-good yields. Georg Thieme Verlag Stuttgart. New York.
- Leao, Raquel A. C.,Def.demoraes, Paula,Pedro, Marcella C. B. C.,Costa, Paulo R. R.
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experimental part
p. 3692 - 3696
(2011/12/16)
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- New approach for the construction of the coumarin frame and application in the total synthesis of natural products
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A new synthetic approach is described for building the coumarin scaffold through the Lewis acid-promoted cyclization of novel aryl 3-(dimethylamino)prop- 2-enoates 2a - 2f. The latter precursors were prepared via aminomethylenation of the corresponding aryl acetates 4a - 4f with the Bredereck reagent. This approach was used for the synthesis of biologically active natural compounds 1a - 1f, through a three-step procedure starting from the corresponding phenols.
- Jerezano, Alberto,Jimenez, Fabiola,Del Carmen Cruz, Maria,Montiel, Luisa E.,Delgado, Francisco,Tamariz, Joaquin
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p. 185 - 198
(2011/04/17)
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- Improved synthesis of coumarins by iron(III)-catalyzed cascade reaction of propiolic acids and phenols
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The reaction of propiolic acids with phenols in the presence of FeClAgOTf catalyst proceeded efficiently in a mixed solvent of trifluoroacetic acid and 1,2-dichloroethane, and provided coumarins in good to high yields. This iron-catalyzed reaction offers a much-improved synthesis of coumarins. Thieme Stuttgart New York.
- Kutubi, Md. Shahajahan,Hashimoto, Takuya,Kitamura, Tsugio
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experimental part
p. 1283 - 1289
(2011/05/19)
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- Yb(OTf)3-catalyzed reactions of 5-alkylidene Meldrum's acids with phenols: One-pot assembly of 3,4-dihydrocoumarins, 4-chromanones, coumarins, and chromones
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The Yb(OTf)3-catalyzed annulation reactions of phenols with 5-alkylidene Meldrum's acids enabled the synthesis of structurally diverse heterocycles in high isolated yields. A series of 4-substituted 3,4-dihydrocoumarins, 2,2-disubstituted 4-chromanones, coumarins, and 2-substituted chromones were readily and efficiently assembled, including the naturally occurring coumarins citropten, scoparone, and ayapin. Addition of phenols to biselectrophilic 5-alkylidene Meldrum's acids proceeded through two distinct multibond-forming modes: Friedel-Crafts C-alkylation/(O-acylation and Friedel-Crafts C-acylation/O-alkylation. The regioselectivity of the catalytic annulation reaction was controlled by the degree of substitution on the alkylidene moiety.
- Fillion, Eric,Dumas, Aaron M.,Kuropatwa, Bryan A.,Malhotra, Neil R.,Sitler, Tamsyn C.
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p. 409 - 412
(2007/10/03)
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- Synthesis of coumarins by Pt-catalyzed hydroarylation of propiolic acids with phenols
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Synthesis of coumarins from phenols and propiolic acids was examined by using a Pt catalyst such as PtCl2/AgOTf, K2PtCl4/AgOTf, and K2PtCl4/AgOAc. Propiolic acid reacted even with less reactive phenols in trifluoroacetic acid to give coumarins and dihydrocoumarins. In the case of substituted propiolic acids, phenylpropiolic acid and 2-octynoic acid, the reactions proceeded selectively to afford coumarins in good to high yields.
- Oyamada, Juzo,Kitamura, Tsugio
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p. 6918 - 6925
(2007/10/03)
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- Natural and synthetic 2,2-dimethylpyranocoumarins with antibacterial activity
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A new efficient synthetic approach to the natural coumarins 5-hydroxyseselin (5), 5-methoxyseselin (3), and (±) cis-grandmarin (9) is described as well as the synthesis of some new derivatives in the 5-methoxyseselin series (10-15). The natural coumarins 7-hydroxyalloxanthyletin (6), alloxanthoxyletin (8), and dipetalolactone (7) have also been obtained as secondary products. The type of fusion of the pyrano ring in all cases has been established by 2D NMR spectroscopy. The compounds have been studied for their in vitro antibacterial activity, which has been compared with that of some previously synthesized seselin derivatives. The most active compounds were 3, 7, 8, 11, and 14. Some structure-activity relationships are discussed.
- Melliou, Eleni,Magiatis, Prokopios,Mitaku, Sofia,Skaltsounis, Alexios-Leandros,Chinou, Efrosini,Chinou, Ioanna
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- Formation of coumarins by palladium(II)-catalyzed reaction of phenols with ethyl acrylates
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The reaction of phenols with ethyl acrylates in the presence of a Pd(OAc)2 catalyst in trifluoroacetic acid did not yield dihydrocoumarins but gave coumarins, in contrast to the reaction of phenols with propiolates. The addition of K2S2O8 as an oxidant increased the yield of coumarins. The reaction of several phenols with ethyl cinnamate, ethyl crotonate, or ethyl acrylate gave the corresponding coumarin derivatives in moderate to good yields. The coumarin formation competed with the oxidative coupling of electron-rich phenols, which reduced the product yield.
- Aoki, Shinya,Oyamada, Juzo,Kitamura, Tsugio
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p. 468 - 472
(2007/10/03)
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- A convenient synthesis of coumarins by palladium(II)-catalyzed reaction of phenols with propiolic acids
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A direct route to coumarin derivatives from phenols and propiolic acids has been developed. Phenols react with propiolic acids in the presence of Pd(OAc)2 as a catalyst to give coumarins in good yields. The simple process occurs under mild conditions without any additives.
- Kotani, Masashi,Yamamoto, Kiyomi,Oyamada, Juzo,Fujiwara, Yuzo,Kitamura, Tsugio
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p. 1466 - 1470
(2007/10/03)
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- Atom economy. Palladium-catalyzed formation of coumarins by addition of phenols and alkynoates via a net C-H insertion
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A strategy to achieve ortho substitution of phenols initiated by an ortho-palladation to create coumarins was examined. Indeed, treatment of alkynoates with electron-rich phenols in the presence of a palladium catalyst and an acid does generate coumarins. The scope of the reaction with respect to the phenol and the alkynoates is defined. With unsymmetrical aromatic substrates, generally good regioselectivity that reflects the HOMO coefficients can be observed. In the course of these studies, numerous important naturally occurring coumarins have been synthesized, including fraxinol methyl ether, ayapin, herniarin, xanthoxyletin, and alloxanthoxyletin. The fact that a Pd(0) is the precatalyst rather than a Pd(+2) species and that an acid that reduces Pd(+2) salts, formic acid, functions better than other carboxylic acids raises doubts about the initial working hypothesis. A novel mechanism involving a palladium phenoxide formed from a hydridopalladium carboxylate and phenol is invoked to rationalize the results.
- Trost, Barry M.,Toste, F. Dean,Greenman, Kevin
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p. 4518 - 4526
(2007/10/03)
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- PdII-Catalyzed Reaction of Phenols with Propiolic Esters. A Single-Step Synthesis of Coumarins
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The intermolecular reaction of phenols with propiolic esters in TFA in the presence of a Pd(OAc)2 catalyst, affording coumarin derivatives, is described. An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin was observed in the reaction of 3,4,5-trimethoxyphenol and ethyl phenylpropiolate with a catalytic amount of Pd(OAc)2. The reaction in the absence of Pd(OAc)2 did not give any coumarin at all. Coumarin derivatives were obtained in high yields in the cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-dimethoxyphenol. Furthermore, the reaction of some phenols with various 2-alkynoates or with diethyl acetylenedicarboxylate gave the corresponding coumarins in good-to-high yields.
- Kitamura, Tsugio,Yamamoto, Kiyomi,Kotani, Masashi,Oyamada, Juzo,Jia, Chengguo,Fujiwara, Yuzo
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p. 1889 - 1895
(2007/10/03)
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- Nucleophilic addition reactions on 3-carbethoxy-5,7-dimethoxycoumarin
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3-Carbethoxy-5,7-dimethoxycoumarin (2) underwent Michael addition and addition-cyclization of some active methylene compounds under different reaction conditions to give the adducts (3-7). Addition of phenylmagnesium bromide onto (2) yielded the tertiary alcohol (8). Addition of ammonia derivatives on (2) afforded the 3-carboxamides (9a-c) and azine (10). Furthermore, alcoholysis and hydrolysis yielded the coumarins (11a-c).
- Hassan,Shiba,Harb,Abou-El-Regal,El-Metwally
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p. 679 - 688
(2007/10/03)
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- Direct synthesis of coumarins by Pd(II)-catalyzed reaction of alkoxyphenols and alkynoates
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Reaction of alkoxyphenols and alkynoates in the presence of a catalytic amount of Pd(OAc)2 in trifluoroacetic acid at room temperature gave coumarin derivatives in high yields. This procedure provides a convenient method for direct synthesis of coumarin derivatives under very mild conditions.
- Oyamada, Juzo,Jia, Chengguo,Fujiwara, Yuzo,Kitamura, Tsugio
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p. 380 - 381
(2007/10/03)
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- Reactions of psoralen radical cations with biological substratest
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The reactions of several psoralen and coumarin radical cations with biological substrates such as nucleotides, amino acids and alkenes that serve as models for unsaturated fatty acids have been examined. The radical cations were generated by laser photoionization of the parent psoralen or coumarin in aqueous buffer in most cases. Easily oxidized substrates such as tyrosine, tryptophan and guanosine monophosphate react with the 8-methoxypsoralen and several methoxy-substituted coumarin radical cations with rate constants in excess of 2 × 109 M-1 s-1. In each case reaction occurs via electron transfer, as demonstrated by the observation of quencher-derived radical cations or radicals by transient absorption spectroscopy. For other substrates such as histidine, methionine and adenosine monophosphate the measured rate constants are significantly slower and vary with the oxidation potential of both the parent psoralen or coumarin and the quencher, again indicative of electron transfer reactivity. Most of the alkenes studied also react with the psoralen or coumarin radical cations via electron transfer, although there is some evidence for addition for linoleic acid. Product studies carried out using both lamp and laser irradiation in the presence of deoxyguanosine as a radical cation trap lead to the formation of characteristic base-derived Type-I (electron transfer) products. This lends support to our previous hypothesis that photoionization occurs via a monophotonic process and is thus relevant to conditions used in clinical phototherapeutic applications of psoralens. The results demonstrate the relevance of electron transfer chemistry to the use of psoralens and related compounds as photoactivated drugs.
- Wood, Paul D.,Mnyusiwalla, Anisa,Chen, Lie,Johnston, Linda J.
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p. 155 - 162
(2007/10/03)
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- A Convenient Synthesis of a Simple Coumarin from Salicylaldehyde and Wittig Reagent (I): A Synthesis of Methoxy- and Hydroxycoumarins
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Reaction of methoxy- and hydroxysalicylaldehydes (1) with phosphorane in diethylaniline under reflux gave only coumarins (3) in high yields except for 3-methoxysalicylaldehyde (1b).It was clarified that methoxy group(s) at C4 and C6 on 1 facilitated the formation of 3.
- Harayama, Takashi,Katsuno, Keiko,Nishioka, Hiromi,Fujii, Masako,Nishita, Yoshitaka,et al.
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p. 613 - 622
(2007/10/02)
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- Enolethers, XVIII. - A Simple Synthesis of Coumarins
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In boiling 1,2-dichloroethane 3-ethoxyacryloyl chloride (1) reacts with phenols 2 to yield 3-ethoxyacrylates 3, which by treatment with conc. sulfuric acid/10percent SO3 cyclize to give coumarins 9 in good yields.The methoxy-substituted compounds 3d and 3k do not react to coumarins 9 with H2SO4/SO3 but with POCl3/H2O at room temperature.
- Ziegler, Thomas,Moehler, Hans,Effenberger, Franz
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p. 373 - 378
(2007/10/02)
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