- Cathodic Regioselective Coupling of Unactivated Aliphatic Ketones with Alkenes
-
A regioselective coupling of aliphatic ketones with alkenes has been realized by cathodic reduction. This reaction enables the formation of ketyl radicals and the activation of challenging alkenes under mild electrolysis conditions, providing an effective protocol for accessing diverse tertiary alcohols with substrate-dependent regioselectivity. The practicability of this reaction is demonstrated by scale-up experiments. The hydrogen source for the products, the migration isomerization of allylarenes, and the applicability of internal alkenes are demonstrated by control experiments.
- Wu, Hongting,Chen, Weihao,Deng, Weijie,Yang, Ling,Li, Xinling,Hu, Yunfei,Li, Yibiao,Chen, Lu,Huang, Yubing
-
supporting information
p. 1412 - 1417
(2022/02/23)
-
- Olefination via Cu-Mediated Dehydroacylation of Unstrained Ketones
-
The dehydroacylation of ketones to olefins is realized under mild conditions, which exhibits a unique reaction pathway involving aromatization-driven C-C cleavage to remove the acyl moiety, followed by Cu-mediated oxidative elimination to form an alkene between the α and β carbons. The newly adopted N′-methylpicolinohydrazonamide (MPHA) reagent is key to enable efficient cleavage of ketone C-C bonds at room temperature. Diverse alkyl- and aryl-substituted olefins, dienes, and special alkenes are generated with broad functional group tolerance. Strategic applications of this method are also demonstrated.
- Dong, Guangbin,Xu, Yan,Zhou, Xukai
-
supporting information
p. 20042 - 20048
(2021/12/03)
-
- Efficient synthesis of styrene derivatives through ethenolysis of renewable propenylbenzenes
-
Functionalized styrenes were obtained by the ethenolysis of renewable 1-propenylbenzenes in a very efficient synthetic pathway. Some of the products are valuable food & flavor ingredients (4-vinylguaiacol) or locust pheromone (4-vinylanisole). The catalysts employed were ruthenium-alkylidene complexes bearing a N-heterocyclic carbene as a ligand, which bulkiness proved to be important for the catalysis output. The judicious choice the reaction conditions was critical to enable near quantitative yields under mild conditions in short reaction times. More strikingly, the catalyst load could be reduced to 0.01 mol%, keeping good conversion and selectivity.
- Avenda?o Villarreal, Jesus A.,Delolo, Fábio G.,Granato, Artur V.,dos Santos, Eduardo N.
-
-
- The first one-pot metathesis-hydroformylation procedure: a straight synthesis of 2-arylpropanals from renewable 1-propenylbenzenes
-
Hydroformylation is a consolidated synthetic tool in the chemical industry, both in commodity and in the fine chemicals industry. Olefin metathesis has been largely employed in the petrochemical sector, and, more recently, in the synthesis of specialty chemicals. Although these reactions may be involved in the same synthetic route for various industrial chemicals, to the best of our knowledge, they have never been combined in a one-pot procedure. As a proof of concept, we have demonstrated in the present work that the ruthenium-catalyzed ethenolysis of renewable 1-propenylbenzenes followed by the rhodium-catalyzed hydroformylation of functionalized styrenes formed in the first step could be done in one pot. The integration of these reactions was not straightforward once the catalyst of the first step interfered with the catalyst of the second step. Under optimized conditions, it was possible to synthesize 2-arylpropanals, a class of compounds valuable as synthetic intermediates to access non-steroidal anti-inflammatory drugs, in overall yields of 85-90%, at low catalyst loadings.
- Avenda?o Villarreal, Jesus Alberto,Delolo, Fábio Godoy,Granato, Artur Vicari,Gusevskaya, Elena Vitalievna,dos Santos, Eduardo Nicolau
-
p. 8007 - 8013
(2021/12/27)
-
- Nickel-Catalyzed Enantioselective Hydroboration of Vinylarenes
-
The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.
- Stanley, Levi M.,Tran, Hai N.
-
supporting information
(2021/12/27)
-
- Ruthenium catalyzed synthesis method of primary amine
-
The invention belongs to the field of organic synthesis, and discloses a ruthenium catalyzed synthesis method of primary amine. A ruthenium complex is taken as a catalyst; and a compound (A) and a compound (B) carry out reactions to obtain a compound (C); wherein R1 represents hydrogen or an alkyl group; R2 represents hydrogen or an alkyl group; R3 represent hydrogen, an alkyl group, or a phenyl group; R4 represent one of following structures shown in the description; n represents 0, 1, 2, or 3; R5 represents an alkyl group, an alkoxyl group, an ester group, a phenyl group, or a halogen atom,when n>=2, at least two R5(s) can be identical or different, m represents 0, 1, 2, or 3, R6 represents an alkyl group, an alkoxyl group, an ester group, or a halogen atom, and when m>=2, at least twoR6(s) can be identical or different. The method has the advantages of simple operation, mild conditions, small using amount of catalysts, wide substrate application range, no need of inert gas, and high yield.
- -
-
Paragraph 0049-0052; 0055-0056
(2020/03/09)
-
- Iron-Catalyzed Direct Julia-Type Olefination of Alcohols
-
Herein, we report an iron-catalyzed, convenient, and expedient strategy for the synthesis of styrene and naphthalene derivatives with the liberation of dihydrogen. The use of a catalyst derived from an earth-abundant metal provides a sustainable strategy to olefins. This method exhibits wide substrate scope (primary and secondary alcohols) functional group tolerance (amino, nitro, halo, alkoxy, thiomethoxy, and S- A nd N-heterocyclic compounds) that can be scaled up. The unprecedented synthesis of 1-methyl naphthalenes proceeds via tandem methenylation/double dehydrogenation. Mechanistic study shows that the cleavage of the C-H bond of alcohol is the rate-determining step.
- Landge, Vinod G.,Babu, Reshma,Yadav, Vinita,Subaramanian, Murugan,Gupta, Virendrakumar,Balaraman, Ekambaram
-
p. 9876 - 9886
(2020/09/03)
-
- Hydrothermal Liquefaction of α-O-4 Aryl Ether Linkages in Lignin
-
By using lignin model compounds with relevant key characteristic structural features, the reaction pathways of α-O-4 aryl ether linkages under hydrothermal conditions are elucidated. Experimental results and computational modeling suggest that the α-O-4 linkages in lignin undergo catalyzed hydrolysis and elimination to give phenolic and alkenylbenzene derivatives as major products in subcritical water. The decreased relative permittivity of water at these high temperatures and pressures facilitates the elimination reactions. The alkyl group on the α-carbon and the methoxy groups on the phenyl rings both have positive effects on the rate of conversion of α-O-4 linkages in native lignin.
- Lui, Matthew Y.,Chan, Bun,Yuen, Alexander K. L.,Masters, Anthony F.,Maschmeyer, Thomas
-
p. 2002 - 2006
(2020/03/05)
-
- Br?nsted Acid Catalyzed Peterson Olefinations
-
A mild and facile Peterson olefination has been developed employing low catalyst loading of the Br?nsted acid HNTf2. The reactions are typically performed at room temperature, with the reaction tolerant to a range of useful functionalities. Furthermore, we have extended this methodology to the synthesis of enynes.
- Britten, Thomas K.,McLaughlin, Mark G.
-
p. 301 - 305
(2019/12/25)
-
- Methylenation for Aldehydes and Ketones Using 1-Methylbenzimidazol-2-yl Methyl Sulfone
-
The methylenation reagent 1-methylbenzimidazol-2-yl methyl sulfone 2 reacts with various aldehydes and ketones in the presence of t-BuOK (room temperature, 1 h) in dimethylformamide to give the corresponding terminal alkenes generally in high yields. For sensitive substrates, the reaction is better carried out at low temperature using sodium hexamethyldisilazide in 1,2-dimethoxyethane. The byproduct is easily removed from the products, and the reaction conditions are mild and practical. Reagent 2 can be easily prepared from commercially available 2-mercaptobenzimidazole 5 in 95% yield without any expensive reagents.
- Ando, Kaori,Oguchi, Mai,Kobayashi, Takahisa,Asano, Haruka,Uchida, Nariaki
-
p. 9936 - 9943
(2020/09/04)
-
- Methoxy-enriched cationic stilbenes as anticancer therapeutics
-
Stilbene-based compounds are largely described for their antioxidant activity. But their use as anticancer chemotherapeutics is hampered by poor pharmacokinetic properties and non-selectivity towards cancer and non-cancer potency. To overcome these drawbacks, twin chain cationic lipid conjugated, methoxy-enriched stilbene derivatives were designed, synthesized and evaluated for their anticancer potency. Our findings reveal that HMSC16, a molecule with the highest number of methoxy groups and with C16-twin chain lipid, is the most potent as well as the most selective anticancer agent when compared to the other synthesized derivatives and commercially available stilbene-based drug, tamoxifen, and resveratrol. To justify these results, we have conducted a series of mechanistic experiments where we found that HMSC16 induced ROS generation, apoptosis, and autophagy by affecting the mitochondrial, lysosomal and nuclear pathways. Further cell cycle analysis data reveals that HMSC16 not only induces cell death but is also involved in the arrest of the cell cycle at the sub-G1 phase. Moreover, HMSC16 showed self-aggregation property owing to a possibly favorable hydrophilic-lipophilic balance. The self-aggregation property of HMSC16 allowed it to entrap hydrophobic drugs, withaferin. With entrapped withaferin, HMSC16 showed additive if not synergistic cell killing effect in HeLa cells. From the above results, we concluded that HMSC16 can be used not just as a drug but also as a drug delivery agent.
- Adhikari, Susanta Sekhar,Banerjee, Rajkumar,Jinka, Sudhakar,Yousuf, Md
-
-
- Ruthenium porphyrin catalysed intermolecular amino-oxyarylation of alkenes to give primary amines: Via a ruthenium nitrido intermediate
-
Ruthenium porphyrin catalysed direct intermolecular amino-oxyarylation of alkenes including styrenes and 1,3-dienes to give primary amines with O-(2,4-dinitrophenyl)hydroxylamine as the amine source was achieved in moderate to good yields under mild reaction conditions. Spectroscopic analyses revealed that a ruthenium nitrido complex was the key reaction intermediate for the amino-oxyarylation reaction.
- Yu, Daohong,Shing, Ka-Pan,Liu, Yungen,Liu, Haiyang,Che, Chi-Ming
-
supporting information
p. 137 - 140
(2019/12/26)
-
- Nickel(ii)-catalyzed direct olefination of benzyl alcohols with sulfones with the liberation of H2
-
A nickel(ii)-catalyzed direct olefination of benzyl alcohols with sulfones to access various terminal and internal olefins with the liberation of hydrogen gas is reported.
- Landge, Vinod G.,Yadav, Vinita,Subaramanian, Murugan,Dangarh, Pragya,Balaraman, Ekambaram
-
supporting information
p. 6130 - 6133
(2019/06/03)
-
- Synthesis of the aglycon of scorzodihydrostilbenes B and D
-
Benzyl- and methyl-protected 2,4-dihydroxyacetophenones are added under ruthenium catalysis to 4-methoxy- and 3,4-dimethoxystyrene in a completely regioselective manner. Thus, oxygenated dihydrostilbenes are obtained that feature the skeleton of scorzodihydrostilbenes – antioxidative agents that were recently isolated from Scorzonera radiata. Selective deprotection liberates the corresponding phenols, among them the aglycon of scorzodihydrostilbenes B and D.
- Weimann, Katja,Braun, Manfred
-
p. 610 - 616
(2019/04/17)
-
- Copper-Catalyzed 1,2-Methoxy Methoxycarbonylation of Alkenes with Methyl Formate
-
Reported here is a copper-catalyzed 1,2-methoxy methoxycarbonylation of alkenes by an unprecedented use of methyl formate as a source of both the methoxy and the methoxycarbonyl groups. This reaction transforms styrene and its derivatives into value-added β-methoxy alkanoates and cinnamates, as well as medicinally important five-membered heterocycles, such as functionalized tetrahydrofurans, γ-lactones, and pyrrolidines. A ternary β-diketiminato-CuI-styrene complex, fully characterized by NMR spectroscopy and X-ray crystallographic analysis, is capable of catalyzing the same transformation. These findings suggest that pre-coordination of electron-rich alkenes to copper might play an important role in accelerating the addition of nucleophilic radicals to electron-rich alkenes, and could have general implications in the design of novel radical-based transformations.
- Budai, Balázs,Leclair, Alexandre,Wang, Qian,Zhu, Jieping
-
supporting information
p. 10305 - 10309
(2019/06/27)
-
- Rapid Access to Ortho-Alkylated Vinylarenes from Aromatic Acids by Dearomatization and Tandem Decarboxylative C-H Olefination/Rearomatization
-
A two-step straightforward method for the preparation of ortho-alkylated vinylarenes from readily available benzoic acids is described. The synthetic route involves the dearomatization of benzoic acids by Birch reduction providing alkylated cyclohexa-2,5-dienyl-1-carboxylic acids. The diene subsequently undergoes a decarboxylative C-H olefination followed by rearomatization to deliver ortho-alkylated vinylarene. Mechanistic studies suggest that a Pd/Ag bimetallic catalytic system is important in the tandem decarboxylative C-H olefination/rearomatization step.
- Tsai, Hung-Chang,Huang, Yen-Hsiang,Chou, Chih-Ming
-
supporting information
p. 1328 - 1332
(2018/03/09)
-
- For treating Parkinson drug Iraq curved tea alkali preparation method of crystal form II (by machine translation)
-
The invention discloses a method for treating Parkinson's drug Iraq curved tea preparation method of alkali crystalline form II, Iraq and curved theophylline with the mixed solvent after mixing, heating to 70 - 90 °C dissolved, then rapidly cooling to 0 - 5 °C, crystallization, to obtain the treatment of Parkinson's drug Iraq curved tea alkali crystalline form II; the invention for the treatment of Parkinson's drug Iraq curved tea alkali crystalline form II, its stability and the prior of the Iraqi curved tea alkali crystalline form II considerable, but yield and purity higher, greatly improves the quality of the product, and can improve its bioavailability, conducive to its pharmaceutical processing and in the use of the drug combination in, at the same time can provide qualitative and quantitative information, to further study the solid curative effect of the medicament has important significance. (by machine translation)
- -
-
Paragraph 0028; 0030
(2018/06/26)
-
- Method of preparing istradefylline crystal form III by means of ball-milling method
-
The invention discloses a method of preparing an istradefylline crystal form III by means of a ball-milling method. The method comprises the following steps: putting istradefylline in a ball-milling tank; adding 100mg of istradefylline into 15-20 mu L tetrahydrofuran; and grinding the mixture at a grinding frequency of 5-10HZ for 60-100min to obtain the tetrahydrofuran crystal form III. The preparation method is novel in process, the reaction yield is improved, and the purity of the finally prepared istradefylline product reaches 99.6% through detection. The istradefylline prepared by the method is matched with a special solvent, and the grinding frequency and the grinding time as a raw material, so that the optical purity of the prepared istradefylline crystal form III is 99.9% or above,and the product quality is improved greatly.
- -
-
Paragraph 0024
(2018/08/04)
-
- Terminal Alkenes from Acrylic Acid Derivatives via Non-Oxidative Enzymatic Decarboxylation by Ferulic Acid Decarboxylases
-
Fungal ferulic acid decarboxylases (FDCs) belong to the UbiD-family of enzymes and catalyse the reversible (de)carboxylation of cinnamic acid derivatives through the use of a prenylated flavin cofactor. The latter is synthesised by the flavin prenyltransferase UbiX. Herein, we demonstrate the applicability of FDC/UbiX expressing cells for both isolated enzyme and whole-cell biocatalysis. FDCs exhibit high activity with total turnover numbers (TTN) of up to 55000 and turnover frequency (TOF) of up to 370 min?1. Co-solvent compatibility studies revealed FDC's tolerance to some organic solvents up 20 % v/v. Using the in-vitro (de)carboxylase activity of holo-FDC as well as whole-cell biocatalysts, we performed a substrate profiling study of three FDCs, providing insights into structural determinants of activity. FDCs display broad substrate tolerance towards a wide range of acrylic acid derivatives bearing (hetero)cyclic or olefinic substituents at C3 affording conversions of up to >99 %. The synthetic utility of FDCs was demonstrated by a preparative-scale decarboxylation.
- Aleku, Godwin A.,Prause, Christoph,Bradshaw-Allen, Ruth T.,Plasch, Katharina,Glueck, Silvia M.,Bailey, Samuel S.,Payne, Karl A. P.,Parker, David A.,Faber, Kurt,Leys, David
-
p. 3736 - 3745
(2018/08/03)
-
- Synthesis and biological evaluation of polyhydroxylated oxindole derivatives as potential antileishmanial agent
-
The devastating appearance of numerous drug-unresponsive strains of Leishmania donovani and severe toxic side effects of conventional antileishmanial therapy necessitates the search for novel leads, to treat visceral leishmaniasis efficiently. The current study deals with the synthesis and biological evaluation of a unique C-5 functionalized oxindole based polyphenol to ascertain its activities against L. donovani infection, in vitro. The polyhydroxylated oxindole derivative (1) was generated by coupling styrene derivatives with 5-bromo bis-arylidene oxindole using Heck coupling reaction. The synthesized molecule 1 was tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Molecule 1 showed promising anti-promastigote and anti-amastigote activities with IC50 values 15 μM and 1 μM, respectively, with no cytotoxicity towards host splenocytes. The results revealed that this compound induced parasite death by promoting oxidative stress, thereby triggering apoptosis.
- Yousuf, Md,Mukherjee, Debarati,Dey, Somaditya,Chatterjee, Saurav,Pal, Abhishek,Sarkar, Biswajyoti,Pal, Chiranjib,Adhikari, Susanta
-
supporting information
p. 1056 - 1062
(2018/02/27)
-
- Synthesis and antiproliferative activity of 3- and 7-styrylcoumarins
-
A series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl-7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids 6e, 10c, and 10d, exhibited the highest activity (IC50- SW480/48h = 6,92; 1,01 and 5,33 μM, respectively) and selectivity (IS48h = >400; 67,8 and 7,2, respectively). In addition, these compounds were able to preserve their activities over time. The results achieved by these hybrids were even better than the lead compounds (coumarin and resveratrol) and the standard drug (5-FU). As regards structure-activity relationship it seems that the location of the styryl group on the coumarin structure and the presence of the hydroxyl group on the phenyl ring were determinant for the activity.
- Herrera-R, Angie,Castrillón, Wilson,Otero, Elver,Ruiz, Esneyder,Carda, Miguel,Agut, Raúl,Naranjo, Tonny,Moreno, Gustavo,Maldonado, Maria Elena,Cardona-G, Wilson
-
p. 1893 - 1905
(2018/06/25)
-
- Selective Oxidation of Aromatic Olefins Catalyzed by Copper(II) Complex in Micellar Media
-
Abstract: The selective oxidation of aromatic olefins 1,2-dimethoxy-4-vinylbenzene (DEVB) and 2-methoxy-4-vinylphenol (MOVP) by H2O2 into 1-(3,4-dime-thoxyphenyl)ethanol (MVA) and 1-(4-hydroxy-3-methoxyphenyl)ethanol (HMOPE) catalyzed by copper(II) complex CuL (L = 6,8,15,17-tetramethyl-7,16-dihydrodibenzo-1,4,8,11-tetraazacyclotetradecine) were achieved in cationic surfactant cetyl trimethylammonium bromide (CTAB), anionic surfactant sodium dodecyl benzene sulfonate (SDBS) and nonionic surfactant Triton X-100 (TX-100) micellar media, respectively. Micelle showed great influence on both reaction rate and selectivity of product. Aromatic olefins could be oxidized into corresponding aromatic ketones in aqueous solution, but into secondary alcohols in micellar media. The combination of TEMPO and CuL/H2O2 resulted in relatively fast reaction rate and S > 96% selectivity of aromatic ketones. The reaction rate constants, k1, k2 and k3 for three oxidation reactions pathways: olefin to ketone, olefin to alcohol and alcohol to ketone were obtained, respectively. The kinetic study indicated that the CuL catalyzed oxidation of olefins by H2O2 to alcohols was a relatively rapid and major reaction and ketone was generated by the direct oxidation of olefins, not by further oxidation of alcohol in micellar media. Graphical Abstract: [Figure not available: see fulltext.].
- Li, Xiao-Hong,Mi, Chun,Liao, Xiao-Hong,Meng, Xiang-Guang
-
p. 2508 - 2514
(2017/09/06)
-
- Efficient synthesis of functionalized olefins by Wittig reaction using Amberlite resin as a mild base
-
A convenient procedure for the synthesis of olefins by the reaction of stabilized, semistabilized, and nonstabilized phosphorous ylides with various aldehydes or ketone using Amberlite resin as a mild base is described. Our developed method offers facile and racemization-free synthesis of α,β-unsaturated amino esters and chiral allylic amine. The developed methodology offers mild reaction conditions, high efficiency, and facile isolation of the final products, a practical alternative to known procedures.
- Valkute, Tushar R.,Aratikatla, Eswar K.,Bhattacharya, Asish K.
-
supporting information
p. 581 - 589
(2017/03/15)
-
- Carboxylation of styrenes with CBr4 and DMSO via cooperative photoredox and cobalt catalysis
-
Cooperative photoredox and cobalt catalyzed carboxylation of styrenes with CBr4 to afford the corresponding α,β-unsaturated carboxylic acids has been realized through radical addition and Kornblum (DMSO) oxidation. DMSO serves as the oxidant, oxygen source and solvent under these photocatalytic conditions.
- Song, Cai-Xia,Chen, Ping,Tang, Yu
-
p. 11233 - 11243
(2017/02/26)
-
- Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents
-
Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.
- Aratikatla, Eswar K.,Valkute, Tushar R.,Puri, Sunil K.,Srivastava, Kumkum,Bhattacharya, Asish K.
-
supporting information
p. 1089 - 1105
(2017/08/03)
-
- Photoinduced, copper-catalyzed three components cyanofluoroalkylation of alkenes with fluoroalkyl iodides as fluoroalkylation reagents
-
In the past few years, Ru and Ir catalyzed photoredox radical coupling reactions have been widely applied in organic synthesis. In contrast, the applications of Cu catalysts in photoredox organic transformations were limited. We here report the first example of photoinduced, Cu-catalyzed three component cyanofluoroalkylation of alkenes by directly using fluoroalkyl iodides as fluoroalkylation reagents.
- Guo, Quanping,Wang, Mengran,Wang, Yanfang,Xu, Zhaoqing,Wang, Rui
-
supporting information
p. 12317 - 12320
(2017/11/20)
-
- Synthesis and Biological Evaluation of N-[2-(4-Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) Tricyclic Analogues as Antimitotic and Antivascular Agents with Potent in Vivo Antitumor Activity
-
Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.9 nM) against the NCI 60 human tumor cell line and significant potency against tubulin assembly (IC50 0.812 μM). In mechanism studies, 16a was shown to block cell cycle in G2/M phase and to disrupt microtubule formation and displayed good antivascular properties as inhibition of cell migration, invasion, and endothelial tube formation. Compound 16a was evaluated in C57BL/6 mouse melanoma B16F10 xenograft model to validate its antitumor activity, in comparison with reference ABT-751 (1). Compound 16a displayed strong in vivo antitumor and antivascular activities at a dose of 5 mg/kg without obvious toxicity, whereas 1 needed a 10-fold higher concentration to reach similar effects.
- Segaoula, Zacharie,Leclercq, Julien,Verones, Valérie,Flouquet, Nathalie,Lecoeur, Marie,Ach, Lionel,Renault, Nicolas,Barczyk, Amélie,Melnyk, Patricia,Berthelot, Pascal,Thuru, Xavier,Lebegue, Nicolas
-
p. 8422 - 8440
(2016/10/03)
-
- Direct Olefination of Alcohols with Sulfones by Using Heterogeneous Platinum Catalysts
-
Carbon-supported Pt nanoparticles (Pt/C) were found to be effective heterogeneous catalysts for the direct Julia olefination of alcohols in the presence of sulfones and KOtBu under oxidant-free conditions. Primary alcohols, including aryl, aliphatic, allyl, and heterocyclic alcohols, underwent olefination with dimethyl sulfone and aryl alkyl sulfones to give terminal and internal olefins, respectively. Secondary alcohols underwent methylenation with dimethyl sulfone. Under 2.5 bar H2, the same reaction system was effective for the transformation of alcohol OH groups to alkyl groups. Structural and mechanistic studies of the terminal olefination system suggested that Pt0 sites on the Pt metal particles are responsible for the rate-limiting dehydrogenation of alcohols and that KOtBu may deprotonate the sulfone reagent. The Pt/C catalyst was reusable after the olefination, and this method showed a higher turnover number (TON) and a wider substrate scope than previously reported methods, which demonstrates the high catalytic efficiency of the present method. Olefination of alcohols: The first heterogeneous catalytic terminal and internal olefination of primary alcohols and methylenation of secondary alcohols with sulfones, a reusable carbon-supported Pt catalyst, and KOtBu is reported (see scheme).
- Hakim Siddiki,Touchy, Abeda Sultana,Kon, Kenichi,Shimizu, Ken-Ichi
-
p. 6111 - 6119
(2016/04/26)
-
- Low-Pressure Cobalt-Catalyzed Enantioselective Hydrovinylation of Vinylarenes
-
An efficient and practical protocol for the enantioselective cobalt-catalyzed hydrovinylation of vinylarenes with ethylene at low (1.2 bar) pressure has been developed. As precatalysts, stable [L2CoCl2] complexes are employed that are activated in situ with Et2AlCl. A modular chiral TADDOL-derived phosphine-phosphite ligand was identified that allows the conversion of a broad spectrum of substrates, including heterocyclic vinylarenes and vinylferrocene, to smoothly afford the branched products with up to 99 % ee and virtually complete regioselectivity. Even polar functional groups, such as OH, NH2, CN, and CO2R, are tolerated.
- Movahhed, Sohajl,Westphal, Julia,Dindaro?lu, Mehmet,Falk, Anna,Schmalz, Hans-Günther
-
supporting information
p. 7381 - 7384
(2016/05/24)
-
- PyFluor: A low-cost, stable, and selective deoxyfluorination reagent
-
We report an inexpensive, thermally stable deoxyfluorination reagent that fluorinates a broad range of alcohols without substantial formation of elimination side products. This combination of selectivity, safety, and economic viability enables deoxyfluorination on preparatory scale. We employ the [18F]-labeled reagent in the first example of a no-carrier-added deoxy-radiofluorination.
- Nielsen, Matthew K.,Ugaz, Christian R.,Li, Wenping,Doyle, Abigail G.
-
supporting information
p. 9571 - 9574
(2015/08/18)
-
- Practical Methylenation Reaction for Aldehydes and Ketones Using New Julia-Type Reagents
-
A new Julia-type methylenation reagent, 1-methyl-2-(methylsulfonyl)benzimidazole (1e), reacts with a variety of aldehydes and ketones in the presence of either NaHMDS (-55 °C to rt) or t-BuOK (rt, 1 h) in DMF to give the corresponding terminal alkenes in high yields. The byproducts are easily removed, and the reaction conditions are mild and practical.
- Ando, Kaori,Kobayashi, Takahisa,Uchida, Nariaki
-
supporting information
p. 2554 - 2557
(2015/05/27)
-
- (E)-Specific direct Julia-olefination of aryl alcohols without extra reducing agents promoted by bases
-
An unprecedented base-promoted direct olefination of aryl alcohols with sulfones via a Julia-type reaction has been described. No extra reductants are needed for Julia reaction since alcohols work as double sources of aldehydes and the hydride. Generally high yields were given for both terminal and highly (E)-selective internal olefins.
- Yao, Chuan-Zhi,Li, Qiang-Qiang,Wang, Mei-Mei,Ning, Xiao-Shan,Kang, Yan-Biao
-
supporting information
p. 7729 - 7732
(2015/05/12)
-
- Selective oxidative cleavage of terminal olefins into aldehydes catalyzed by copper(II) complex
-
A simple method for oxidative C=C bond cleavage of terminal olefins to aldehydes with H2O2 catalyzed by copper(II) complex LCu consisted of copper(II) and macrocyclic ligand 5,7,12,14-tetramethyl-1,4,8,11-tetraazacyclotetradeca-4,7,11,14-tetraene (L) was described. This study indicated that the copper(II) complex displayed excellent catalytic ability for the selective oxidation of terminal olefins to aldehydes with high selectivity (S > 90%) in CH3CN at 30 °C. The possible catalytic reaction mechanism of oxidation of terminal olefins was discussed.
- Mi, Chun,Meng, Xiang-Guang,Liao, Xiao-Hong,Peng, Xiao
-
p. 69487 - 69492
(2015/09/01)
-
- A transition-metal-free Heck-type reaction between alkenes and alkyl iodides enabled by light in water
-
A transition-metal-free coupling protocol between various alkenes and non-activated alkyl iodides has been developed by using photoenergy in water for the first time. Under UV irradiation and basic aqueous conditions, various alkenes efficiently couple with a wide range of non-activated alkyl iodides. A tentative mechanism, which involves an atom transfer radical addition process, for the coupling is proposed.
- Liu, Wenbo,Li, Lu,Chen, Zhengwang,Li, Chao-Jun
-
supporting information
p. 6170 - 6174
(2015/06/08)
-
- Direct catalytic olefination of alcohols with sulfones
-
The synthesis of terminal as well as internal olefins was achieved by the one-step olefination of alcohols with sulfones catalyzed by a ruthenium pincer complex. Furthermore performing the reaction with dimethyl sulfone under mild hydrogen pressure provides a direct route for the replacement of alcohol hydroxy groups by methyl groups in one step.
- Srimani, Dipankar,Leitus, Gregory,Ben-David, Yehoshoa,Milstein, David
-
supporting information
p. 11092 - 11095
(2015/03/30)
-
- Heck, Sonogashira, and Hiyama reactions catalyzed by palladium nanoparticles stabilized by tris-imidazolium salt
-
Palladium nanoparticles, prepared by the hydrogenation of Pd(dba) 2 in the presence of a tris-imidazolium iodide as stabilizer, act as an efficient catalyst for Heck and copper-free Sonogashira reactions with a range of aryl iodides and bromides at 0.2 mol-% Pd loading. Moreover, we describe a convenient protocol for the fluoride-free Hiyama coupling of vinylsilanes with aryl iodides that involves the use of sodium hydroxide as promoter in a methanol/water mixture. Under the developed conditions, one-pot, double Heck and Hiyama-Heck reactions are successfully achieved.
- Planellas, Marc,Moglie, Yanina,Alonso, Francisco,Yus, Miguel,Pleixats, Roser,Shafir, Alexandr
-
supporting information
p. 3001 - 3008
(2014/05/20)
-
- Correlating lignin structural features to phase partitioning behavior in a novel aqueous fractionation of softwood Kraft black liquor
-
In this work, a set of softwood lignins were recovered from a Kraft black liquor using a novel pH-based fractionation process involving sequential CO 2 acidification and separation of the solvated aqueous lignin fraction. These recovered lignin fractions were characterized with respect to properties that may be responsible for their phase partitioning behavior as well as properties that may render the lignins more suitable for materials applications. Lignin fractions were recovered between a pH range of 12.8 and 9.5 with the bulk of the lignin (90%) recovered between a pH of 11.1 and 10.0. While all the fractions were found to consist primarily of lignin as validated by sample methoxyl content, the first fractions to phase separated were found to be especially enriched in aliphatic extractives and polysaccharides. From the bulk of the lignin that was recovered between a pH of 11.1 and 10.0 a number of noteworthy trends were discernible from the data. Specifically, the phenolic hydroxyl content was found to exhibit a strong negative correlation to the fractionation pH and exhibited a nearly 50% increase with recovery at decreasing pH, while the GPC-estimated molecular weights and 13C NMR-estimated β-O-4 content showed strong positive correlations to the pH at recovery. The aliphatic hydroxyl content exhibited minimal differences between recovery conditions. Overall, these results suggest that this fractionation approach can generate lignin fractions enriched in select physical or structural properties that may be important for their application as feedstocks for renewable chemicals or materials.
- Stoklosa, Ryan J.,Velez, Julian,Kelkar, Shantanu,Saffron, Christopher M.,Thies, Mark C.,Hodge, David B.
-
supporting information
p. 2904 - 2912
(2013/10/08)
-
- Resveratrol derived butyrylcholinesterase inhibitors
-
Novel polyhydroxylated (E)-stilbenes were synthesized by Mizoroki-Heck reactions and tested for their ability to inhibit the enzymes acetyl- and butyrylcholinesterase. Several of them are good inhibitors of butyrylcholinesterase; one of them carrying an extra fluorine substituent is a 94-fold stronger inhibitor of butyrylcholinesterase than of acetylcholinesterase. Novel polyhydroxylated (E)-stilbenes synthesized by Mizoroki-Heck reactions were tested for their ability to inhibit the enzymes acetyl- and butyrylcholinesterase. Several of them were found to be good inhibitors of butyrylcholinesterase. One of them carrying an extra fluorine substituent is a 94-fold stronger inhibitor of butyrylcholinesterase than of acetylcholinesterase.
- Csuk, Rene,Albert, Sabrina,Kluge, Ralph,Stroehl, Dieter
-
p. 499 - 503
(2013/07/26)
-
- Synthesis and radical scavenging activities of resveratrol analogs
-
Highly substituted polyhydroxylated (E)-stilbenes were synthesized by Mizoroki-Heck reactions and tested for their ability to act as radical scavenger. One of the 56 stilbenes included in this study and investigated in DPPH assays gave an SC50 value of 11.0 μM, hence exhibiting an about 9.3 times higher activity than resveratrol. As shown in a photometric SRB assay using mouse NiH 3T3 fibroblasts, this compound is not cytotoxic up to concentrations of 30 μM. Highly substituted polyhydroxylated (E)-stilbenes synthesized by Mizoroki-Heck reactions were tested for their ability to act as radical scavengers. One of the 56 stilbenes included exhibited about 9.3 times higher activity than resveratrol. At concentrations 30 μM, this compound was not cytotoxic.
- Csuk, Rene,Albert, Sabrina,Siewert, Bianka
-
p. 504 - 510
(2013/07/26)
-
- Isomerizing ethenolysis as an efficient strategy for styrene synthesis
-
A shrinking chain: A bimetallic system consisting of [{Pd(μ-Br)(tBu 3P)}2] and a ruthenium metathesis catalyst has been found to efficiently promote the cross-metathesis between substituted alkenes and ethylene, while continuously migrating the double bond along the alkenyl chain (see scheme). When alkenylarenes, such as the natural products eugenol, safrol, or estragol, were treated with this catalyst under an ethylene atmosphere, they were cleanly converted into the corresponding styrenes and propylene gas. Copyright
- Baader, Sabrina,Ohlmann, Dominik M.,Goossen, Lukas J.
-
supporting information
p. 9807 - 9810
(2013/08/23)
-
- Flow Chemistry Syntheses of Styrenes, Unsymmetrical Stilbenes and Branched Aldehydes
-
Two tandem flow chemistry processes have been developed. A single palladium-catalysed Heck reaction with ethylene gas provides an efficient synthesis for functionalised styrenes. Through further elaboration the catalyst becomes multi-functional and performs a second Heck reaction providing a single continuous process for the synthesis of unsymmetrical stilbenes. In addition, the continuous, rhodium-catalysed, hydroformylation of styrene derivatives with syngas affords branched aldehydes with good selectivity. Incorporation of an in-line aqueous wash and liquid-liquid separation allowed for the ethylene Heck reaction to be telescoped into the hydroformylation step such that a single flow synthesis of branched aldehydes directly from aryl iodides was achieved. The tube-in-tube semi-permeable membrane-based gas reactor and liquid-liquid separator both play an essential role in enabling these telescoped flow processes.
- Bourne, Samuel L.,O'Brien, Matthew,Kasinathan, Sivarajan,Koos, Peter,Tolstoy, Paeivi,Hu, Dennis X.,Bates, Roderick W.,Martin, Benjamin,Schenkel, Berthold,Ley, Steven V.
-
p. 159 - 172
(2013/03/13)
-
- An approach to the synthesis of tetrahydroisoquinoline alkaloids by alkene hydroamination: Synthesis of coralydine
-
The protoberberine alkaloid coralydine was synthesized in a short sequence by a strategy including an intramolecular alkene hydroamination as the key step, followed by a Pictet-Spengler cyclization. Georg Thieme Verlag Stuttgart · New York.
- Pouilhès, Annie,Baltaze, Jean-Pierre,Kouklovsky, Cyrille
-
supporting information
p. 1805 - 1808
(2013/09/12)
-
- Enantioselective nickel-catalyzed hydrocyanation of vinylarenes using chiral phosphine-phosphite ligands and TMS-CN as a source of HCN
-
Anti-headache chemistry: In the presence of a tailored modular P,P ligand the nickel-catalyzed addition of HCN, generated in situ from TMS-CN, to styrene derivatives proceeds with an unprecedented level of stereocontrol (up to 97 % ee) to give 2-aryl-acetonitriles, for example, the depicted precursor of Ibuprofen. Copyright
- Falk, Anna,Goederz, Anna-Lena,Schmalz, Hans-Guenther
-
supporting information
p. 1576 - 1580
(2013/03/13)
-
- Iron-catalyzed, highly regioselective synthesis of α-aryl carboxylic acids from styrene derivatives and CO2
-
The iron-catalyzed hydrocarboxylation of aryl alkenes has been developed using a highly active bench-stable iron(II) precatalyst to give α-aryl carboxylic acids in excellent yields and with near-perfect regioselectivity. Using just 1 mol % FeCl2, bis(imino)pyridine 6 (1 mol %), CO 2 (atmospheric pressure), and a hydride source (EtMgBr, 1.2 equiv), a range of sterically and electronically differentiated aryl alkenes were transformed to the corresponding α-aryl carboxylic acids (up to 96% isolated yield). The catalyst was found to be equally active with a loading of 0.1 mol %. Preliminary mechanistic investigations show that an iron-catalyzed hydrometalation is followed by transmetalation and reaction with the electrophile (CO2).
- Greenhalgh, Mark D.,Thomas, Stephen P.
-
supporting information; experimental part
p. 11900 - 11903
(2012/09/07)
-
- Synthesis and antimicrobial activity of (E) stilbene derivatives
-
Plants use multiple defence mechanisms comprising both constitutive and inducible barriers to prevent entering of phytopathogenic micro-organisms. In many plant species one of the most efficient responses to combat attacking microbes is the rapid synthesis of antimicrobial low molecular weight phytoalexins, for example, resveratrol, 3,5,4′-trihydroxystilbene (1). Resveratrol and its natural derivatives, however, display only moderate antimicrobial effects. Nevertheless, resveratrol may be a useful lead structure for the chemical synthesis of antimicrobials. In this study, several series of stilbenes have been synthesized, starting from the aldehydes using Wittig reactions to access the corresponding styrenes that were subjected to Mizoroki-Heck reactions to yield the stilbenes in good yields. The stilbenes were tested in an agar diffusion assay against several bacteria and fungi. For some of these compounds the inhibiting zones for bacteria and fungi were comparable with those of the antibiotics tetracycline, streptomycin, ampicillin, or kanamycin, directed against prokaryotes, and nourseothricin or hygromycin controlling fungi, respectively.
- Albert, Sabrina,Horbach, Ralf,Deising, Holger B.,Siewert, Bianka,Csuk, René
-
supporting information; experimental part
p. 5155 - 5166
(2011/10/04)
-
- Synthesis and biological evaluation of isosteric analogs of mandipropamid for the control of oomycete pathogens
-
A series of isosteric analogs of mandipropamid were designed and synthesized via 'click chemistry'. The amide bond of mandipropamid was substituted by a 1,2,3-triazole functional group. The bioassay results have indicated that some of the title compounds exhibited moderate fungicidal activity against Pseudoperonospora cubensis, and the activity has been systematically studied as a function of molecular structure. The low activity of the mandipropamid analog that contains a lipid chain is likely due to the presence of a weak hydrogen bond donor in the 1,2,3-triazole. Furthermore, we have performed the molecular modeling and found that N-methylamide could be more effective than amide as the surrogates to 1,2,3-triazole, which ultimately leads to a longer distance (1.1A longer) between the two substitutes in the 1,4-disubstituted 1,2,3-triazole compound.
- Su, Na,Wang, Zhen-Jun,Wang, Li-Zhong,Zhang, Xiao,Dong, Wei-Li,Wang, Hong-Xue,Li, Zheng-Ming,Zhao, Wei-Guang
-
scheme or table
p. 101 - 111
(2012/06/01)
-
- A synergic blend of newly isolated pseudomonas mandelii KJLPB5 and [hmim]Br for chemoselective 2° aryl alcohol oxidation in H2O2: Synthesis of aryl ketone or aldehydes via sequential dehydration-oxidative C=C cleavage
-
Pseudomonas mandelii KJLPB5 is reported for the oxidation of aryl alcohols in ionic liquid [hmim]Br (1-hexyl-3-methyl imidazolium bromide) with H 2O2. With a slight alteration of reaction conditions, the developed protocol leads either to (i) chemoselective oxidation of 2° aryl alcohols over 1° and aliphatic counterparts or (ii) direct one pot-two step sequential conversion of 2° aryl alcohols into corresponding one or two carbons shorter aryl aldehydes through oxidative cleavage pathway, thus providing a new facet to metal-free oxidations. The key operational parameters such as substrate concentration, incubation temperature, incubation time, ionic liquid type and ionic liquid concentration are also optimized. Graphical Abstract: [Figure not available: see fulltext.]
- Sharma, Nandini,Sharma, Upendra K.,Salwan, Richa,Kasana, Ramesh C.,Sinha, Arun K.
-
scheme or table
p. 616 - 622
(2012/01/14)
-
- Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer
-
A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC50 0.59 μM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC50 70 nM) and 84 (IC50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC 50 1.7 μM and 0.27 μM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.
- Sun, Bin,Hoshino, Juma,Jermihov, Katie,Marler, Laura,Pezzuto, John M.,Mesecar, Andrew D.,Cushman, Mark
-
experimental part
p. 5352 - 5366
(2010/09/05)
-
- Synthesis of alkaloids of Galipea officinalis by alkylation of an α-amino nitrile
-
A new synthetic approach directed towards the synthesis of naturally occurring 2-alkyl-tetrahydroquinolines is described. The C-C bonds in the α position relative to the nitrogen atom were formed by the reversal of the polarity of the C=N bond of α-amino nitrile 6, which was prepared electrochemically from 1-(phenylethyl)-tetrahydroquinoline. A NaBH 4-mediated reductive decyanation process furnished benzylic amines 16a-d as mixtures of diastereomers (50-60% de). The catalytic hydrogenolysis of these amines was performed in the presence of Pearlman's catalyst to give the tetrahydroquinolines 17a-d in yields ranging from 70% to 95%. Methylation of the free nitrogen atom afforded the title compounds 1-4 in 70-90% yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Shahane, Saurabh,Louafi, Fadila,Moreau, Julie,Hurvois, Jean-Pierre,Renaud, Jean-Luc,Van De Weghe, Pierre,Roisnel, Thierry
-
body text
p. 4622 - 4631
(2009/05/07)
-
- Attempts to mimic key bond-forming events associated with the proposed biogenesis of the pentacyclic lamellarins
-
The pyrrole-tethered veratroles 16 and 27 each engage in PIFA-induced oxidative cyclization reactions to give compounds 22 and 29, respectively, which incorporate a key tricyclic fragment associated with the title natural products. In contrast, the corresponding catechols 11 and 12 only produce polymeric materials on subjection to analogous reaction conditions. Efforts to study lactone ring formation by the oxidative cyclization of catechol 30 and veratrole 38 have been thwarted by an inability to prepare the former substrate and decomposition of the latter. The reported conversions 44 ? 45 and 46 ? 47 suggest that a C2-carboxy group attached to the pyrrole ring can ?direct' the oxidative cyclization of N-tethered aryl groups. The acquisition of compound 22 by the means described herein provides an adventitious and concise route to the racemic modification of the pyrrolo[2,1-a]isoquinoline alkaloid crispine A (52). CSIRO 2008.
- Axford, Lorraine C.,Holden, Kate E.,Hasse, Katrin,Banwell, Martin G.,Steglich, Wolfgang,Wagler, Joerg,Willis, Anthony C.
-
-