- Annulation-retro-Claisen cascade of bifunctional peroxides for the synthesis of lactone natural products
-
A new and highly efficient annulation-retro-Claisen cascade, which involves the [4 + 1] or [5 + 1] annulation of α-benzoylacetates with bielectrophilic peroxides and a subsequent debenzoylation process under mild basic conditions, has been developed for the rapid construction of valuable tetrahydrofuran- and dihydropyran-2-carboxylates in good yields. By employing the new reaction, the unified total synthesis of γ- and δ-lactone natural products such as (±)-tanikolide, (±)-goniothalamins, (±)-7-epi-goniodiol, and (±)-plakolide A has been accomplished in 4-7 steps.
- Hu, Lin,Li, Jialin,Li, Xuemin,Xu, Qianlan
-
supporting information
p. 274 - 277
(2022/01/03)
-
- Electrochemical Oxidative Cyclization: Synthesis of Polysubstituted Pyrrole from Enamines
-
A conceptually novel method for the preparation of pyrrole is described by electrochemical-oxidation-induced intermolecular annulation via enamines. In a simple undivided cell, based on a sodium acetate-facilitated, polysubstituted pyrrole derivations has been facilely synthesized under external oxidant-free condition. This electrosynthetic approach providing an environmentally benign protocol for C?C bond cross-coupling and oxidative annulation, which features unparalleled broad scope of substrates and practicality.
- Chen, Zhiwei,Shi, Guang,Tang, Wei,Sun, Jie,Wang, Wenxing
-
supporting information
p. 951 - 955
(2021/02/03)
-
- Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of β-Ketoesters
-
Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method
- Chen, Jiajia,Joseph, Devaneyan,Xia, Yuanzhi,Lee, Sunwoo
-
p. 5943 - 5953
(2021/04/02)
-
- A Hammett Study of Clostridium acetobutylicum Alcohol Dehydrogenase (CaADH): An Enzyme with Remarkable Substrate Promiscuity and Utility for Organic Synthesis
-
Described is a physical organic study of the reduction of three sets of carbonyl compounds by the NADPH-dependent enzyme Clostridium acetobutylicum alcohol dehydrogenase (CaADH). Previous studies in our group have shown this enzyme to display broad substrate promiscuity, yet remarkable stereochemical fidelity, in the reduction of carbonyl compounds, including α-, β- and γ-keto esters (d -stereochemistry), as well as α,α-difluorinated-β-keto phosphonate esters (l -stereochemistry). To better mechanistically characterize this promising dehydrogenase enzyme, we report here the results of a Hammett linear free-energy relationship (LFER) study across three distinct classes of carbonyl substrates; namely aryl aldehydes, aryl β-keto esters and aryl trifluoromethyl ketones. Rates are measured by monitoring the decrease in NADPH fluorescence at 460 nm with time across a range of substrate concentrations for each member of each carbonyl compound class. The resulting v 0 versus [S] data are subjected to least-squares hyperbolic fitting to the Michaelis-Menton equation. Hammett plots of log(V max) versus σ X yield the following Hammett parameters: (i) for p -substituted aldehydes, ρ = 0.99 ± 0.10, ρ = 0.40 ± 0.09; two domains observed, (ii) for p -substituted β-keto esters ρ = 1.02 ± 0.31, and (iii) for p -substituted aryl trifluoromethyl ketones ρ = -0.97 ± 0.12. The positive sign of ρ indicated for the first two compound classes suggests that the hydride transfer from the nicotinamide cofactor is at least partially rate-limiting, whereas the negative sign of ρ for the aryl trifluoromethyl ketone class suggests that dehydration of the ketone hydrate may be rate-limiting for this compound class. Consistent with this notion, examination of the 13 C NMR spectra for the set of p -substituted aryl trifluo romethyl ketones in 2percent aqueous DMSO reveals significant formation of the hydrate (gem -diol) for this compound family, with compounds bearing the more electron-withdrawing groups showing greater degrees of hydration. This work also presents the first examples of the CaADH-mediated reduction of aryl trifluoromethyl ketones, and chiral HPLC analysis indicates that the parent compound α,α,α-trifluoroacetophenone is enzymatically reduced in 99percent ee and 95percent yield, providing the (S)-stereoisomer, suggesting yet another compound class for which this enzyme displays high enantioselectivity.
- Berkowitz, David B.,Kudalkar, Gaurav P.,Lee, Joshua D.,Tiwari, Virendra K.
-
supporting information
p. 237 - 247
(2020/02/18)
-
- Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis
-
Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.
- Liu, Hao-Nan,Cao, Hao-Qiang,Cheung, Chi Wai,Ma, Jun-An
-
supporting information
p. 1396 - 1401
(2020/02/22)
-
- Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
-
Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
- Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
-
p. 2214 - 2231
(2020/03/06)
-
- Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting multiple protein kinases as anticancer agents
-
A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Several compounds showed very potent antiproliferative activities toward both cell lines and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide (8a–8i, 9a–9m) and urea (10a–10d, 11a–11d) with diverse hydrophobic moieties. One of the most potent inhibitor 10d, 1-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-(2-oxo-2,3-dihydro-1H-thieno [3,4-b][1,4]diazepin-4-yl)phenyl)urea was found to be very potent inhibitor of multi-protein kinases including FMS kinase (IC50 = 3.73 nM) and is a promising candidate for further development in therapeutics for cancer.
- Lee, Junghun,Jung, Hoyong,Kim, Minjung,Lee, Eunkyu,Im, Daseul,Aman, Waqar,Hah, Jung-Mi
-
p. 1628 - 1637
(2018/02/21)
-
- Pyrazole alcohol compound, pharmaceutical composition thereof and application thereof to drugs
-
The invention discloses a 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound, a tautomer thereof, a pharmaceutical composition thereof and application thereof to drugs. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound has double effects of resisting platelet aggregation and protecting nerve cells, and comprises a compound as shown in the formula (I), a tautomer (Ia) thereof, or a stereoisomer, a geometrical isomer, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt or prodrug as shown in the description. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound and the pharmaceutical composition thereof provided by the invention can be used for preparing drugs for prevention and/or treatment and/or auxiliary treatment of cerebral apoplexy, cardiovascular and cerebrovascular diseases, senile dementia and complications thereof caused by thrombosis and excessive free radicals.
- -
-
Paragraph 0128; 0138
(2018/10/19)
-
- THIENODIAZEPINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
-
The present invention relates to novel thienodiazepine derivatives or pharmaceutically acceptable salts thereof, and a pharmaceutical composition including the same. The thienodiazepine derivatives or pharmaceutically acceptable salts thereof exhibit selective inhibition activities against protein kinases such as c-Kit, FLT3, FMS, LYN, RAF1, VEGFR3, PDGFRa, PDGFRb, RET, etc., and thus can be used as a pharmaceutical composition for prevention or treatment of abnormal cell growth diseases.
- -
-
Paragraph 0128-0130
(2018/03/01)
-
- Bromide-Mediated C-H Bond Functionalization: Intermolecular Annulation of Phenylethanone Derivatives with Alkynes for the Synthesis of 1-Naphthols
-
Bromide-mediated intermolecular annulation of phenylethanone derivatives with alkynes has been developed, which allows for the regioselective formation of polysubstituted 1-naphthols. The usage of readily available bromine catalyst, broad substrate scope, and mild conditions make this protocol very practical. Mechanistic investigations reveal that the bromination of phenylethanone derivatives occurs to yield bromo-substituted intermediates, which react in situ with alkynes to furnish the desired 1-naphthols.
- Lu, Tao,Jiang, Ya-Ting,Ma, Feng-Ping,Tang, Zi-Jing,Kuang, Liu,Wang, Yu-Xuan,Wang, Bin
-
supporting information
p. 6344 - 6347
(2017/12/08)
-
- Regioselective Synthesis of Dihydrothiophenes and Thiophenes via the Rhodium-Catalyzed Transannulation of 1,2,3-Thiadiazoles with Alkenes
-
A method for the regioselective synthesis of a wide range of dihydrothiophenes was developed from the rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with aliphatic, aromatic, and heteroaromatic alkenes. Tandem rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with alkenes followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation was also demonstrated for the one-pot regioselective synthesis of various thiophenes. Advantages of the present method include a broad substrate scope, wide functional group compatibility, and high regioselectivity.
- Son, Jeong-Yu,Kim, Jonghye,Han, Sang Hoon,Kim, Sung Hong,Lee, Phil Ho
-
supporting information
p. 5408 - 5411
(2016/11/06)
-
- 2 - (3-cyano-4-alkoxy) phenyl-4-substituted thiazole-5- formic acid class compound, composition and its preparation and use
-
The invention relates to a 2-(3-cyano-4-alkoxy) phenyl-4-substituted thiazole-5-formic acid compound which has xanthine oxidase inhibitory activity and is shown in a general formula I, a composition and preparation methods thereof. The invention also relates to applications of the compound and the composition thereof to preparation of medicaments for treating and/or preventing hyperuricemia and gout diseases. In the formula I, R2 is substituted or unsubstituted phenyl or a substituted or unsubstituted heteroaromatic radical, R1 is a substitutive aliphatic group of a straight chain or a branched chain, substituted or unsubstituted alicyclic hydrocarbonyl or substituted or unsubstituted aryl alkyl and A is an oxygen atom, a sulfur atom or a nitrogen atom.
- -
-
Paragraph 0163; 0165
(2016/10/07)
-
- 1,5-Diketones Synthesis via Three-Component Cascade Reaction
-
A mild and efficient cascade synthesis of 1,5-diketones from readily available N,N-dicyclohexylmethylamine, 1,3-dicarbonyl compounds, and trifluoromethyl β-diketones has been developed. This cascade reaction occurs via an oxidation/Mannich reaction/Cope elimination/Michael addition/retro-Claisen reaction sequence, and provides multiple C-C bond formations in one pot. In addition, exquisite chemoselectivity is achieved in the reaction between 1,3-dicarbonyl compounds and trifluoromethyl β-diketones.
- Xing, Li-Juan,Lu, Tao,Fu, Wei-Li,Lou, Mei-Mei,Chen, Bo,Wang, Zhi-Shen,Jin, Yang,Li, Dan,Wang, Bin
-
supporting information
p. 3076 - 3080
(2015/11/03)
-
- Design, synthesis and RON receptor tyrosine kinase inhibitory activity of new head groups analogs of LCRF-0004
-
New heteroarylcarboxamide head groups substituted with two aromatic rings analogs of thieno[3,2-b]pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent inhibitors of RON tyrosine kinase with various level of selectivity for c-Met RTK were obtained.
- Raeppel, Franck,Raeppel, Stéphane L.,Therrien, Eric
-
p. 3810 - 3815
(2015/08/24)
-
- Access to β-keto esters by palladium-catalyzed carbonylative coupling of aryl halides with monoester potassium malonates
-
New tricks for an old dog: The Pd-catalyzed carbonylative α-arylation of monoethyl potassium malonates with aryl bromides and reactive aryl chlorides provides a simple and direct route to aryl β-ketoesters. Because only stoichiometric amounts of carbon monoxide are employed, the method is ideal for the introduction of carbon isotopes into more complex structures. Copyright
- Korsager, Signe,Nielsen, Dennis U.,Taaning, Rolf H.,Skrydstrup, Troels
-
supporting information
p. 9763 - 9766
(2013/09/23)
-
- Ligand steric and electronic effects on β-ketiminato neutral nickel(II) olefin polymerization catalysts
-
A series of novel neutral nickel complexes 3a-g and 4a-d bearing the β-ketiminato ligands [(2,6-iPr2C6H 3)N=CHCHC(R)O]Ni(R′)(L) (for 3a-g, R′ = Me, L = Py, and R = tBu (3a), Ph (3b), 1-naphthyl (3c), 9-anthryl (3d), PhNMe 2(p) (3e), PhOMe(p) (3f), PhCF3(p) (3g); for 4a-d, R′ = Ph, L = PPh3, and tBu (4a), Ph (4b), 1-naphthyl (4c), 9-anthryl (4d)) have been synthesized and characterized. The molecular structures of 3b-d,f,g and 4a,c were further confirmed by X-ray crystallographic analysis. These complexes were employed in ethylene polymerization to systematically investigate ligand steric and electronic effects on the catalytic properties, including activity, molecular weight (MW), and branching number of the polyethylene obtained. The complexes bearing more bulky ligands showed higher activities and produced more branched polyethylene. Electron-deficient ligands were found to increase the catalytic activity, decrease the MW, and enhance the branching content of the polyethylene. In addition, phosphine NiII-Ph complexes 4a-d proved to be more active than the corresponding pyridine NiII-Me complexes 3a-d, probably due to the easier dissociation of PPh3 relative to a pyridine from a nickel center.
- Song, Dong-Po,Shi, Xin-Cui,Wang, Yong-Xia,Yang, Ji-Xing,Li, Yue-Sheng
-
experimental part
p. 966 - 975
(2012/04/10)
-
- One-pot synthesis of β-keto esters and preparation of 3-ketopalmitoyl-CoA
-
β-Keto esters were synthesized from acyl chlorides and sodium ethyl acetoacetate in EtOH using a simple one-pot, one-step' method. The deacetylation of α-acetyl β-keto ester to β-keto ester was performed simply, by heating the reaction mixture at reflux for 12 hours, without the addition of additional reagents (e.g., NHl, NH MeOH, or NaOH). One of the β-keto esters prepared using this method was ethyl 3-oxohexadecanoate, a key intermediate in the synthesis of 3-ketopalmitoyl coenzyme A (3-oxohexadecanoyl coenzyme A), a potential substrate of the biologically important enzyme 17β-hydroxysteroid dehydrogenase type 12. Georg Thieme Verlag Stuttgart ? New York.
- Ko?ak, Urban,Kova?, Andreja,Gobec, Stanislav
-
experimental part
p. 1609 - 1612
(2012/08/07)
-
- Syntheses of phenylpyrazolodiazepin-7-ones as conformationally rigid analogs of aminopyrazole amide scaffold and their antiproliferative effects on cancer cells
-
Recently, we have reported the syntheses and antiproliferative activities of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives on melanoma cells. As a continuous work for antiproliferative agents in melanoma, here we report the synthesis of conformationally rigid analogs, phenyl-6,8- dihydropyrazolo[3,4-b][1,4]diazepin-7(1H)-one derivatives 7a-g, 8a-o and their antiproliferative activities against A375P melanoma cell line and U937 hematopoietic cell line. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(3-(1-benzyl-7-oxo-1,6,7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl) -4-chloro-3-(trifluoro methyl)benzamide-amino-1-(4-methoxybenzyl)-1H-pyrazol-4- yl)-5-(3-(4-chloro-3-(trifluoromethyl) phenyl) ureido)-2-methylbenzamide (7b) exhibited potent activities (GI50 = 0.43 μM and 0.06 μM) on both cell lines. It has been further confirmed to be a potent and selective Raf kinases inhibitor and also mild inhibitor of PI3Kα.
- Kim, Hyangmi,Kim, Minjung,Lee, Junghun,Yu, Hana,Hah, Jung-Mi
-
p. 6760 - 6767
(2012/01/13)
-
- Unusual anion effects in the iron-catalyzed formation of 3-hydroxyacrylates from aromatic aldehydes and ethyl diazoacetate
-
Due to the lability of one of the CO ligands in irans-[Fe(PNP)(CO) 2Cl]+ this compound is an efficient catalyst for the coupling of a series of aromatic aldehydes with ethyl diazoacetate (EDA), which give, in most cases, selectively 3-hydroxyacrylates rather than β-oxo esters. This reaction is strongly dependent on the nature of the counterion, Whereas with BF4- the reaction proceeds with conversions up to 90%, in the case of the counterions NO3-, CF 3COO-, CF3SO3-, SbF 6-, and BAr'4- [Ar' = 3,5-(CF 3)2C6H3] no reaction took place. In the case of PF6- only up to 20% conversion was achieved. A conceivable mechanism for the coupling of aromatic aldehydes with EDA was established by means of DFT/B3LYP calculations, which allowed the rationalization of both the chemoselectivity and the role of the counterions.
- Alves, Luis Goncalo,Dazinger, Georg,Veiros, Luis F.,Kirchner, Karl
-
experimental part
p. 3160 - 3166
(2011/01/05)
-
- Synthesis and evaluation of the α-glucosidase inhibitory activity of 3-[4-(phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives
-
In the course of studies directed toward the discovery of novel non-sugar α-glucosidase inhibitors for the treatment of diabetes, a series of 3-[4-(phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives was synthesized and evaluated as α-glucosidase inhibitors. Most compounds showed good inhibitory activity with IC50 values ranging from 0.0645?μM to 26.746?μM. 7-Hydroxy-6-methoxy-3-[4-(4-methylphenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one 7u manifested the most potent inhibitory activity with an IC50 value of 0.0645 μM.
- Wang, Shaojie,Yan, Jufang,Wang, Xiaoyan,Yang, Zhuo,Lin, Fengwei,Zhang, Tingjian
-
experimental part
p. 1250 - 1255
(2010/04/26)
-
- Molybdenum(VI) dichloride dioxide catalyzed synthesis of β-keto esters by C-H insertion of ethyl diazoacetate into aldehydes
-
Synthesis of β-keto esters by condensing various aldehydes with ethyl diazoacetate is achieved by using molybdenum(VI) dichloride dioxide. Aromatic, aliphatic, and heterocyclic aldehydes are successfully condensed with ethyl diazoacetate to obtain corresponding β-keto esters in high yields at room temperature.
- Jeyakumar, Kandasamy,Chand, Dillip Kumar
-
p. 1685 - 1687
(2008/12/21)
-
- Selective synthesis of α-substituted β-keto esters from aldehydes and diazoesters on mesoporous silica catalysts
-
The titled reactions are effectively catalyzed on mesoporous silica MCM-41 but not on amorphous silica prepared from the same starting materials as those of MCM-41. The ordered porous structure was essential to generate the acid catalysis. Planting of Al or Ti ion improved not only the catalytic activity but also the tolerance to basic functional groups of substrates. The catalytic activity of Al- or Ti-MCM-41 was better than that of SnCl2 and NbCl5 in the homogeneous phase. In particular, Al (or Ti)-MCM-41 was characteristically active for the reaction of aldehydes with α-substituted diazoesters to give 2-substituted-3-oxo propionic acid esters.
- Murata, Hiroaki,Ishitani, Haruro,Iwamoto, Masakazu
-
p. 4788 - 4791
(2008/12/22)
-
- Structure-activity relationships of 1,4-dihydropyridines that act as enhancers of the vanilloid receptor 1 (TRPV1)
-
Vanilloid agonists such as capsaicin activate ion flux through the TRPV1 channel, a heat- and ligand-gated cation channel that transduces painful chemical or thermal stimuli applied to peripheral nerve endings in skin or deep tissues. We have probed the SAR of a variety of 1,4-dihydropyridine (DHP) derivatives as novel 'enhancers' of TRPV1 activity by examining changes in capsaicin-induced elevations in 45Ca2+-uptake in either cells ectopically expressing TRPV1 or in cultured dorsal root ganglion (DRG) neurons. The enhancers increased the maximal capsaicin effect on 45Ca2+-uptake by typically 2- to 3-fold without producing an action when used alone. The DHP enhancers contained 6-aryl substitution and small alkyl groups at the 1 and 4 positions, and a 3-phenylalkylthioester was tolerated. Levels of free intracellular Ca2+, as measured by calcium imaging, were also increased in DRG neurons when exposed to the combination of capsaicin and the most efficacious enhancer 23 compared to capsaicin alone. Thus, DHPs can modulate TRPV1 channels in a positive fashion.
- Roh, Eun Joo,Keller, Jason M.,Olah, Zoltan,Iadarola, Michael J.,Jacobson, Kenneth A.
-
experimental part
p. 9349 - 9358
(2009/04/06)
-
- A novel synthetic method for β-keto esters
-
A novel synthetic method for the preparation of β-keto esters has been developed. α-Phenylseleno acetate was treated with LDA to produce a selenium-stabilised carbanion, which reacted with aldehydes, followed by selenoxide syn-elimination, to give β-keto esters.
- Qian, Hao,Ge, Chunrong,Huang, Xian
-
p. 160 - 161
(2008/02/03)
-
- Substitution of acyl for acetyl with N-acylbenzotriazoles catalyzed by samarium triiodide
-
Catalyzed by samarium triiodide (SmI3), substitution of acyl with N-acylbenzotriazoles for acetyl in acetoacetic esters and acetylacetone proceeds smoothly under neutral conditions in open air, affording the corresponding β-keto esters and β-diketones in good yields. Copyright Taylor & Francis Group, LLC.
- Zou, Xuefei,Jia, Xiaofei,Wang, Xiaoxia,Xie, Guanqun
-
p. 1617 - 1625
(2008/02/01)
-
- Microwave assisted rapid and efficient synthesis of aryl methyl ketones and β-keto esters using Meldrum's acid
-
Microwave mediated rapid and efficient synthesis of aryl methyl ketones and β-keto esters from acyl Meldrum's acid by hydrolysis and alcoholysis, respectively, has been reported.
- More,Mahulikar
-
p. 823 - 825
(2007/10/03)
-
- Preparation of polystyrene-supported α-seleno acetate and application to solid-phase synthesis of β-keto esters
-
A novel polystyrene-supported α-seleno acetate has been developed. This novel resin was treated with LDA to produce a selenium-stabilized carbanion, which reacted with aldehydes, followed by selenoxide syn-elimination to give β-keto esters. Georg Thieme Verlag Stuttgart.
- Qian, Hao,Huang, Xian
-
p. 1547 - 1548
(2007/10/03)
-
- Niobium(V) chloride-catalyzed C-H insertion reactions of α-diazoesters: Synthesis of β-keto esters
-
Aldehydes react readily with ethyl diazoacetate in the presence of 5 mol% of NbCl5 in dichloromethane to produce the corresponding β-keto esters in good yields with high selectivity. This method is very useful for the preparation of β-keto esters from both electron-rich as well as electron-deficient aromatic aldehydes under mild reaction conditions.
- Yadav,Subba Reddy,Eeshwaraiah,Reddy
-
p. 875 - 878
(2007/10/03)
-
- Acid-catalyzed reactions of aromatic aldehydes with ethyl diazoacetate: An investigation on the synthesis of 3-hydroxy-2-arylacrylic acid ethyl esters
-
Several commercial Lewis acids, including those of the Bronsted type, specifically HBF4·OEt2, are able to catalyze the reaction between aromatic aldehydes and ethyl diazoacetate to produce 3-hydroxy-2-arylacrylic acid ethyl esters and 3-oxo-3-arylpropanoic acid ethyl esters. Reactions catalyzed by the iron Lewis acid [(η5-C 5H5)Fe+(CO)2(THF)]BF 4- (i.e., 1) have the best yields and greatest ratio of 3-hydroxy-2-arylacrylic acid ethyl ester. The product distribution of 1 is not affected in the presence of Proton Sponge, but is dependent on temperature and the nature of the substrate aldehyde, whereas the activity of HBF 4-OEt2 is affected by the presence of Proton Sponge and is reactive at temperatures as low as -78 °C. Consequently, both 1 and HBF4·OEt2 are valuable catalysts in producing important 3-hydroxy-2-arylacrylic acid ethyl esters as precursors to biologically active compounds.
- Dudley, Matthew E.,Morshed, Monzur,Brennan, Courtney L.,Islam, M. Shahidul,Ahmad, M. Syarhabil,Atuu, Mary-Rose,Branstetter, Bryan,Hossain, M. Mahmun
-
p. 7599 - 7608
(2007/10/03)
-
- PROCESS FOR PRODUCING FUSED IMIDAZOLE COMPOUND, REFORMATSKY REAGENT IN STABLE FORM, AND PROCESS FOR PRODUCING THE SAME
-
The present invention provides an industrially advantageous process for producing a steroid C17,20 lyase inhibitor represented by the general formula (I): and a Reformatsky reagent in a stable form suitable for the process.In the present invention, a compound represented by the general formula (I) is produced by reducing a specific β-hydroxy ester compound derivative or a salt thereof obtained from a specific carbonyl compound in a Reformatsky reaction in the presence of a metal hydride complex and a metal halide, and then subjecting it to a ring-closing reaction. In the above Reformatsky reaction, it is useful to use a stable solution of a compound represented by the general formula BrZnCH2COOC2H5 or a crystal of the compound which is represented by the formula (BrZnCH2COOC2H5·THF)2.
- -
-
-
- MEDICINAL COMPOSITION
-
The present invention is composed of a pharmaceutical composition for the therapy of nephritis which comprises an amide derivative represented by the following formula [1] or pharmaceutically acceptable salt thereof, as an active ingredient: ???wherein R1 and R2 may be the same or different and each is hydrogen, alkyl which may be substituted, acyl, aryl which may be substituted, or an aromatic heterocyclic group which may be substituted; R3, R4, R5 and R6 may be the same or different and each is hydrogen, halogen, hydroxy, amino which may be substituted, alkyl which may be substituted, alkoxy or nitro and the like; and R7 represents cyclic amino which may be substituted or azabicycloalkylamino which may be substituted. The pharmaceutical composition of the invention is useful for the therapy of nephritis.
- -
-
-
- AMIDE DERIVATIVES AND DRUG COMPOSITIONS
-
The present invention is composed of an amide derivative represented by the following formula [1] or pharmaceutically acceptable salt thereof: ???wherein R1 and R2 may be the same or different and each is hydrogen, alkyl which may be substituted, acyl, aryl which may be substituted, or an aromatic heterocyclic group which may be substituted; R3, R4, R5, and R6 may be the same or different and each is hydrogen, halogen, hydroxy, amino which may be substituted, alkyl which may be substituted, alkoxy, or nitro and the like; and R7 represents cyclic amino which may be substituted or azabicycloalkylamino which may be substituted, and a pharmaceutical composition which comprises it as an active ingredient. The compound of the invention is useful as an inhibitor of TGF-β production or an antagonist of TGF-β.
- -
-
-
- Lewis acid-catalyzed reactions of ethyl diazoacetate with aldehydes. Synthesis of α-formyl esters by a sequence of aldol reaction and 1,2- nucleophilic rearrangement
-
Ethyl diazoacetate reacts with a variety of aldehydes in the presence of a Lewis acid catalyst to give either β-keto esters or α-formyl esters, the types of products mainly depending upon the nature of Lewis acid catalysts employed. Reactions catalyzed by Lewis acids such as SnCl2 and SnCl4 provide β-keto esters via nucleophilic 1,2-hydride migration, while those catalyzed by trimethylsilyl triflate give α-formyl esters via migration of the substituent of the aldehyde. Reaction mechanisms are discussed.
- Kanemasa, Shuji,Kanai, Toshio,Araki, Takahiro,Wada, Eiji
-
p. 5055 - 5058
(2007/10/03)
-
- High-temperature rearrangements of 2-acylisoxazol-5(2H)-ones and related oxazoles
-
2-Acyl-3-arylisoxazol-5(2H)-ones give 2-alkyl(aryl)-4-aryloxazoles in good yields at 540°C under flash vacuum pyrolysis conditions, but at higher temperatures the expected oxazoles are accompanied by increasing amounts of isomeric 2,5-disubstituted oxazoles, as well as anilides and decomposition products of the 2,4-disubstituted oxazole. The rearrangement mechanisms have been studied by the use of 13C labelled substrates and p-substituted 3-arylisoxazolones. The 2,5-disubstituted oxazoles are considered to arise from 1H-azirines, and the anilides from the nitrone ketene isomer of the acylisoxazolone.
- Clark, Adrian D.,Ha, Uyen T.,Prager, Rolf H.,Smith, Jason A.
-
p. 1029 - 1033
(2007/10/03)
-
- Iron Lewis Acid Catalyzed Reactions of Aromatic Aldehydes with Ethyl Diazoacetate: Unprecedented Formation of 3-Hydroxy-2-arylacrylic Acid Ethyl Esters by a Unique 1,2-Aryl Shift
-
The iron Lewis acid [η5-(C5H5)Fe(CO)2(THF)]BF 4 (1) was found to catalyze reactions of ethyl diazoacetate (EDA) and aromatic aldehydes, yielding 3-hydroxy-2-arylacrylie acid ethyl esters and the corresponding β-keto esters. According to the literature, this is the first report of the formation of enol esters from EDA and aromatic aldehydes. The yield of the enol esters increased with electronrich aldehydes. With 2,4-dimethoxybenzaldehyde the only product isolated was the corresponding enol ester in 80% yield. However, in the presence of electron-deficient aldehydes such as p-nitrobenzaldehyde, formation of enol ester decreased to 32%. The most unique feature of these reactions is that enol esters are formed by an unusual 1,2-aryl shift, from a possible intermediate 8, which in turn is formed from the reaction of the iron aldehyde complex 7 and EDA.
- Mahmood, Syed J.,Hossain, M. Mahmun
-
p. 3333 - 3336
(2007/10/03)
-
- Simple and high yielding syntheses of β-keto esters catalysed by zeolites
-
Simple and high yielding syntheses of several β-keto esters, catalysed by zeolite Hβ are reported. The methods developed include condensation of aldehydes with ethyl diazoacetate and transesterification of β-keto esters with primary, secondary, allylic and benzylic alcohols etc., all catalysed by Hβ. It was further observed that under microwave irradiation the yields of many aromatic β-keto esters were enhanced appreciably.
- Balaji,Chanda, Bhanu M.
-
p. 13237 - 13252
(2007/10/03)
-
- Group transfer reactions using benzimidazolides
-
Transfer of aroyl group from N-aroylbenzimidazoles 1a-d to the enolates generated from ethyl acetoacetate 2 and acetylacetone 3 has been achieved successfully. in-situ Cleavage of acetyl group of the acetylated products has also been observed.
- Karnik, A. V.,Rane, J. P.
-
p. 1191 - 1193
(2007/10/03)
-
- A safe, economical method for the preparation of β-oxo esters
-
A high yield, economical method for preparation of β-oxo esters has been developed involving the reaction of acid chlorides with potassium ethyl malonate using a magnesium chloride-triethylamine base system in either acetonitrile or ethyl acetate solvents. The method is suitable for the preparation of high purity β-oxo esters in the laboratory and also in large scale production.
- Clay,Collom,Karrick,Wemple
-
p. 290 - 292
(2007/10/02)
-
- Enamines; 44. 2-Acyl-1,1-diamino-ethenes. A New Source of Methylketones, β-Keto Amides and β-Keto Esters
-
A general synthesis of 2-acyl-1,1-diamino-ethenes by reaction of 1,1-dimorpholino- and 1,1-dipiperidino-ethenes with aliphatic and aromatic acyl chlorides and their utilization as a source of methylketones, β-keto amides and β-keto esters is reported.
- Armati, Antonella,Ruggieri, Pietro De,Rossi, Elisabetta,Stradi, Riccardo
-
p. 573 - 576
(2007/10/02)
-
- FACILE SYNTHESIS OF β-KETOESTERS BY A COUPLING REACTION OF THE REFORMATSKY REAGENT WITH ACYL CHLORIDES CATALYZED BY A PALLADIUM COMPLEX
-
β-Ketoesters were obtained in good yields by the reaction of the Reformatsky reagent with acyl chlorides catalyzed by a palladium complex under mild conditions.
- Sato, Toshio,Itoh, Toshiyuki,Fujisawa, Tamotsu
-
p. 1559 - 1560
(2007/10/02)
-