- Cu(II)-promoted oxidative C-N bond cleavage of N-benzoylamino acids to primary aryl amides
-
A novel protocol for CuCl2-promoted oxidative C-N bond cleavage of N-benzoyl amino acids was developed. It is the first example of using accessible amino acid as an ammonia synthetic equivalent for the synthesis of primary aryl amides via CuCl2-promoted oxidative C-N bond cleavage reaction. The present protocol shows excellent functional group tolerance and provides an alternative method for the synthetic of primary aryl amides in 84-96% yields.
- Zhou, Liandi,Liu, Wei,Zhao, Yongli,Chen, Junmin
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- Palladium-Catalyzed Allenamide Carbopalladation/Allylation with Active Methine Compounds
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A palladium-catalyzed allenamide carbopalladation/allylation with active methine compounds has been developed. Various indoles and isoquinolinones bearing a quaternary carbon center were achieved with good efficiency, a broad substrate scope and good functional group tolerance. This reaction underwent cascade oxidative addition, carbopalladation, and allylic alkylation, and two new C-C bonds were formed in one pot.
- Zhu, Xiaoyi,Li, Ruibo,Yao, Hequan,Lin, Aijun
-
supporting information
p. 4630 - 4634
(2021/06/28)
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- Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes
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A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation and carbonylation from readily available starting materials has been developed. This modular multicomponent hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range of unactivated alkenes to produce a wide variety of unsymmetrical dialkyl ketones bearing a functionalized α-stereocenter, including enantioenriched chiral α-aryl ketones and α-amino ketones. It uses chiral bisoxazoline as a ligand, silane as a reductant, chloroformate as a safe CO source, and a racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester of a protected α-amino acid as the alkylation reagent. The benign nature of this process renders this method suitable for late-stage functionalization of complex molecules.
- Chen, Jian,Zhu, Shaolin
-
supporting information
p. 14089 - 14096
(2021/09/13)
-
- 4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae
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A current issue of antimicrobial therapy is the resistance to treatment with worldwide consequences. Thus, the identification of innovative targets is an intriguing challenge in the drug and development process aimed at newer antimicrobial agents. The state-of-art of anticholera therapy might comprise the reduction of the expression of cholera toxin, which could be reached through the inhibition of carbonic anhydrases expressed in Vibrio cholerae (VchCAα, VchCAβ, and VchCAγ). Therefore, we focused our interest on the exploitation of sulfonamides as VchCA inhibitors. We planned to design and synthesize new benzenesulfonamides based on our knowledge of the VchCA catalytic site. The synthesized compounds were tested thus collecting useful SAR information. From our investigation, we identified new potent VchCA inhibitors, some of them displayed high affinity toward VchCAγ class, for which few inhibitors are currently reported in literature. The best interesting VchCAγ inhibitor (S)-N-(1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)furan-2-carboxamide (40) resulted more active and selective inhibitor when compared with acetazolamide (AAZ) as well as previously reported VchCA inhibitors.
- Mancuso, Francesca,De Luca, Laura,Bucolo, Federica,Vrabel, Milan,Angeli, Andrea,Capasso, Clemente,Supuran, Claudiu T.,Gitto, Rosaria
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p. 3787 - 3794
(2021/10/20)
-
- Organocatalytic asymmetric [4+2] cyclization of 2-benzothiazolimines with azlactones: Access to chiral benzothiazolopyrimidine derivatives
-
An organocatalytic asymmetric domino Mannich/cyclization reaction between 2-benzothiazolimines with azlactones has been successfully developed. With the bifunctional squaramide catalyst, this formal [4+2] cyclization occurs with good to high yields and excellent stereoselectivities (up to 99% ee, >20?:?1 dr), providing an efficient and mild access to chiral benzothiazolopyrimidines bearing adjacent tertiary and quaternary stereogenic centers.
- Ni, Qijian,Wang, Xuyang,Xu, Fangfang,Chen, Xiaoyun,Song, Xiaoxiao
-
supporting information
p. 3155 - 3158
(2020/03/23)
-
- Asymmetric construction of dihydrobenzofuran-2,5-dione derivatives via desymmetrization of p-quinols with azlactones
-
The desymmetrization of p-quinols through a chiral bisguanidinium hemisalt catalyzed enantioselective Michael addition/lactonization cascade reaction with azlactones was reported. 3-Amino-benzofuran-2,5-diones containing a chiral amino acid residue were achieved with up to 99% ee and >19?:?1 dr. An exploration of the structure of the catalyst bisguanidinium was undertaken, revealing a bifunctional catalytic model.
- Xie, Lihua,Dong, Shunxi,Zhang, Qian,Feng, Xiaoming,Liu, Xiaohua
-
supporting information
p. 87 - 90
(2019/01/03)
-
- GRANZYME B DIRECTED IMAGING AND THERAPY
-
Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
- -
-
Page/Page column 82; 98
(2019/09/04)
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- Colocalization Strategy Unveils an Underside Binding Site in the Transmembrane Domain of Smoothened Receptor
-
We unveiled an underside binding site on smoothened receptor (SMO) by a colocalization strategy using two structurally complementary photoaffinity probes derived from a known ligand Allo-1. Docking study and structural dissection identified key interactions within the site, including hydrogen bonding, πinteractions, and hydrophobic interactions between Allo-1 and its contacting residues. Taken together, our results reveal the molecular base of Allo-1 binding and provide a basis for the design of new-generation ligands to overcome drug resistance.
- Zhou, Fang,Ding, Kang,Zhou, Yiqing,Liu, Yang,Liu, Xiaoyan,Zhao, Fei,Wu, Yiran,Zhang, Xianjun,Tan, Qiwen,Xu, Fei,Tan, Wenfu,Xiao, Youli,Zhao, Suwen,Tao, Houchao
-
supporting information
p. 9983 - 9989
(2019/11/03)
-
- Palladium-catalyzed asymmetric decarboxylative allylation of azlactone enol carbonates: Fast access to enantioenriched α-allyl quaternary amino acids
-
We report a fast protocol for the synthesis of enantioenriched quaternary 4-allyl oxazol-5-ones. The key step is a Pd-catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α-amino acids. The use of (R,R)-DACH-phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4-allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step.
- Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,De Lorenzi, Ersilia,Colombo, Lino
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p. 732 - 741
(2019/01/09)
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- METHODS OF TREATING OR PREVENTING COGNITIVE IMPAIRMENT USING INDANE ACETIC ACID DERIVATIVES BASED ON APOE4 GENOTYPE
-
The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of cognitive disorders based on the ApoE4 genotype of human subjects.
- -
-
Paragraph 0508-0510
(2018/06/15)
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- METHODS OF DOSE ADMINISTRATION FOR TREATING OR PREVENTING COGNITIVE IMPAIRMENT USING INDANE ACETIC ACID DERIVATIVES
-
The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of cognitive disorders.
- -
-
Paragraph 0511; 0512
(2018/06/15)
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- Dynamic Kinetic Resolution of N-Protected Amino Acid Esters via Phase-Transfer Catalytic Base Hydrolysis
-
Asymmetric base hydrolysis of α-chiral esters with synthetic small-molecule catalysts is described. Quaternary ammonium salts derived from quinine were used as chiral phase-transfer catalysts to promote the base hydrolysis of N-protected amino acid hexafluoroisopropyl esters in a CHCl3/NaOH (aq) via dynamic kinetic resolution, providing the corresponding products in moderate to good yields (up to 99%) with up to 96:4 er. Experimental and computational mechanistic studies using DFT calculation and pseudotransition state (pseudo-TS) conformational search afforded a TS model accounting for the origin of the stereoselectivity. The model suggested π-stacking and H-bonding interactions play essential roles in stabilizing the TS structures.
- Yamamoto, Eiji,Wakafuji, Kodai,Furutachi, Yuho,Kobayashi, Kaoru,Kamachi, Takashi,Tokunaga, Makoto
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p. 5708 - 5713
(2018/05/30)
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- Reactivity of α-Amino Acids in the Reaction with Esters in Aqueous–1,4-Dioxane Media
-
The kinetics of the reaction of a series of α-amino acids with 4-nitrophenyl acetate, 4-nitrophenyl benzoate, and 2,4,6-trinitrophenyl benzoate in aqueous 1,4-dioxane medium has been studied. Kinetics of the reactions involving 4-nitrophenyl acetate and 2,4,6-trinitrophenyl benzoate has complied with the Br?nsted dependence and revealed linear correlation between rate constant logarithm and the energy difference of the frontier orbitals of α-amino acids anions.
- Kochetova,Kustova,Kuritsyn
-
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- A Flexible Polyphosphate-Driven Regeneration System for Coenzyme A Dependent Catalysis
-
Coenzyme A (CoA) is a common cofactor in biochemical reactions, and CoA-dependent enzymes catalyze essential steps in anabolism and catabolism. This complex molecule also plays an important role in the synthesis of many high-value products, such as synthetic antibiotics, vitamins, pheromones, and biopolymers. Nevertheless, the synthetic potential for biocatalytic processes cannot be fully exploited owing to the lack of an efficient regeneration system. Here, we report an acyl-CoA regeneration system with integrated adenosine triphosphate (ATP) regeneration that is based on inexpensive polyphosphate as the single energy source. In the four-enzyme cascade, two cofactors, acyl-CoA and ATP, are each regenerated up to 2000 times. The applicability for different acyl donors and acceptors is shown by HPLC analysis. Owing to its flexibility toward virtually all relevant substrates, the system has the potential to make CoA-dependent reactions more accessible for chemical synthesis in vitro.
- Mordhorst, Silja,Maurer, Alice,Popadi?, Désirée,Brech, Johanna,Andexer, Jennifer N.
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p. 4164 - 4168
(2017/10/23)
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- Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid
-
A novel method for the synthesis of trisubstituted oxazoles via a one-pot oxazole synthesis/Suzuki–Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki–Miyaura coupling with boronic acids provided the corresponding 2,4,5-trisubstituted oxazoles in good yields.
- Yamada, Kohei,Kamimura, Naoto,Kunishima, Munetaka
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p. 1478 - 1485
(2017/08/02)
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- Palladium-Catalyzed Ortho-Alkoxylation of N-Benzoyl α-Amino Acid Derivatives at Room Temperature
-
An efficient palladium-catalyzed ortho-alkoxylation of N-benzoyl α-amino acid derivatives at room temperature has been explored. This novel transformation, using amino acids as directing groups, Pd(OAc)2 as catalyst, alcohols as the alkoxylation reagents, and PhI(OAc)2 as the oxidant, showed wide generality, good functional tolerance, and high monoselectivity and regioselectivity.
- Li, Shuangjie,Zhu, Wei,Gao, Feng,Li, Chunpu,Wang, Jiang,Liu, Hong
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p. 126 - 134
(2017/04/26)
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- Synthesis of Hydrazones from Amino Acids and their Antimicrobial and Cytotoxic Activities
-
Hydrazones 6a–6n were synthesized from different amino acids with various aldehydes under reflux in methanol/ethanol. The structures of synthesized compounds were ascertained by elemental analysis and spectroscopic techniques. A comparative study of the antimicrobial activity and cytotoxicity was carried out of the N-protected amino acids, their esters, hydrazides, and the respective hydrazones, providing good results in cytotoxicity studies.
- Abid, Obaid-Ur-Rahman,Khatoon, Ghamama,Arfan, Muhammad,Sajid, Imran,Langer, Peter,Rehman, Wajid,Rahim, Fazal,Yasir, Muhammad,Waqar, Muhammad,Haleem, Kashif Syed
-
p. 1079 - 1087
(2017/09/26)
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- Cu(II)-promoted oxidative C-N bond cleavage of N-benzoylamino acids to primary aryl amides
-
A novel protocol for CuCl2-promoted oxidative C-N bond cleavage of N-benzoyl amino acids was developed. It is the first example of using accessible amino acid as an ammonia synthetic equivalent for the synthesis of primary aryl amides via CuCl2-promoted oxidative C-N bond cleavage reaction. The present protocol shows excellent functional group tolerance and provides an alternative method for the synthetic of primary aryl amides in 84-96percent yields.
- Chen, Junmin,Liu, Wei,Zhao, Yongli,Zhou, Liandi
-
-
- Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives
-
Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.
- Wang, Tianli,Yu, Zhaoyuan,Hoon, Ding Long,Phee, Claire Yan,Lan, Yu,Lu, Yixin
-
supporting information
p. 265 - 271
(2016/01/25)
-
- Synthesis of an enantiopure thioester as key substrate for screening the sensitivity of penicillin binding proteins to inhibitors
-
The synthesis of the enantiopure thioester (R)-2-(2-benzamidopropanoylthio)acetic acid was developed. After the exploration of several activation methods, reaction conditions were found for the formation of the thioester bond in the presence of propylphosphonic anhydride with high enantioselectivity (ee > 99%). The thioester activity of Penicillin Binding Proteins is helpful in research programs looking for new lead structures to overcome the problem of bacterial resistance.
- Simon, Justine F.,Bouillez, André,Frère, Jean-Marie,Luxen, André,Zervosen, Astrid
-
-
- Hybrid Diphenylalkyne-Dipeptide Oligomers Induce Multistrand β-Sheet Formation
-
Functionalized diphenylalkynes provide a template for the presentation of protein-like surfaces composed of multistrand β-sheets. The conformational properties of three-, four-, and seven-stranded systems have been investigated in the solid- and solution-state. This class of molecule may be suitable for the mediation of therapeutically relevant protein-protein interactions. β-Sheets: Functionalized diphenylalkynes provide a template for the presentation of protein-like surfaces composed of multi-strand β-sheets. The conformational properties of three-, four-, and seven-stranded systems have been investigated in the solid- and solution-state. This class of molecule may be suitable for the mediation of therapeutically relevant protein-protein interactions.
- Ross, Jonathan E.,Knipe, Peter C.,Thompson, Sam,Hamilton, Andrew D.
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p. 13518 - 13521
(2015/09/22)
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- Peptide backbone cleavage by α-amidation is enhanced at methionine residues
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Cleavage reactions at backbone loci are one of the consequences of oxidation of proteins and peptides. During α-amidation, the Cα-N bond in the backbone is cleaved under formation of an N-terminal peptide amide and a C-terminal keto acyl peptide. On the basis of earlier works, a facilitation of α-amidation by the thioether group of adjacent methionine side chains was proposed. This reaction was characterized by using benzoylmethionine and benzoyl alanylmethionine as peptidemodels. The decomposition of benzoylated amino acids (benzoyl-methionine, benzoyl-alanine, and benzoyl-methionine sulfoxide) to benzamide in the presence of different carbohydrate compounds (reducing sugars, Amadori products, and reductones) was studied during incubation for up to 48h at 80 °C in acetate-buffered solution (pH 6.0). Small amounts of benzamide (0.3-1.5mol%) were formed in the presence of all sugars and from all benzoylated species. However, benzamide formation was strongly enhanced, when benzoyl methionine was incubated in the presence of reductones and Amadori compounds (3.5-4.2mol%). The reaction was found to be intramolecular, because α-amidation of a similar 4-methylbenzoylated amino acid was not enhanced in the presence of benzoyl-methionine and carbohydrate compounds. In the peptide benzoyl-alanyl-methionine, α-amidation at themethionine residue is preferred over α-amidation at the benzoyl peptide bond. We propose here a mechanism for the enhancement of α-amidation at methionine residues.
- Hellwig, Michael,L?bmann, Katja,Orywol, Tom
-
-
- Catalyst and method for producing the same
-
PROBLEM TO BE SOLVED: To provide a method for producing an amide compound from a primary alcohol and at least one selected from a primary amine, a secondary amine and derivatives of those under relatively mild conditions with high selectivity and a high conversion ratio.SOLUTION: A method for producing an amide compound comprises a step of obtaining the amide compound from a primary alcohol and at least one selected from a primary amine, a secondary amine and derivatives of those, in the presence of a catalyst comprising a carrier formed by crosslinking a crosslinkable functional group of a styrene-based polymer having a side chain containing the crosslinkable functional group, and a nanosize cluster and carbon black supported on the carrier, wherein the nanosize cluster is at least one selected from a nanosize gold cluster and a nanosize cluster of gold and at least one group 8 metal selected from iron, cobalt and nickel.
- -
-
Paragraph 0099
(2016/11/07)
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- Catalyst-free synthesis of N -(1,7-dioxotetrahydropyrazolo[1,2-a]pyrazol-2- yl)benzamide derivatives by 1,3-dipolar cycloaddition and rearrangement
-
N-(1,7-Dioxotetrahydropyrazolo[1,2-a]pyrazol-2-yl)-benzamide derivatives, a novel class of compounds, were synthesized by 1,3-dipolar cycloaddition of azomethine imines with azlactones and subsequent rearrangement. The reaction can be completed rapidly under mild conditions without a catalyst. Georg Thieme Verlag Stuttgart New York.
- Liu, Wenjing,Xu, Yu,Sun, Xingxia,Lu, Dapeng,Guo, Lijuan
-
supporting information
p. 1093 - 1096
(2014/05/20)
-
- Bronsted acid accelerated Pd-catalyzed direct asymmetric allylic alkylation of azlactones with simple allylic alcohols: A practical access to quaternary allylic amino acid derivatives
-
A Bronsted acid accelerated Pd-catalyzed asymmetric allylic alkylation of azlactones with simple allylic alcohols under mild reaction conditions has been realized, which provides a direct and readily scalable approach for the synthesis of all-carbon quaternary allylic amino acid derivatives in excellent yields and good enantioselectivities. (Chemical Equation Presented).
- Zhou, Hui,Yang, Huameng,Liu, Muwen,Xia, Chungu,Jiang, Gaoxi
-
supporting information
p. 5350 - 5353
(2015/01/09)
-
- Organocatalyzed asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones: Synthesis of α,α-disubstituted α-amino acid derivatives
-
The first asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones catalyzed by cinchona alkaloid derived bifunctional thiourea catalysts was developed. A series of α,α-disubstituted α-amino acid derivatives bearing a quaternary stereocenter at the α-position were obtained in high yields with excellent diastereo- and enantioselectivities (up to -20:1 dr and 99% ee). In addition, the trichloromethyl moiety in these adducts was identified as a good leaving group.
- Zhang, Jinlong,Liu, Xihong,Wu, Chongyang,Zhang, Panpan,Chen, Jianbo,Wang, Rui
-
supporting information
p. 7104 - 7108
(2015/01/16)
-
- Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition
-
Some new di- and trisubstituted imidazole-4-carboxylates were prepared from amidoacetic acids 3 in the present report. The key step to establish such imidazole- 4-carboxylates stemmed from the PBu3-mediated [3+2] cycloaddition between in situ-generated Δ2-oxazolinone 4 and ethyl cyanoformate6. Our results indicated that trisubstituted imidazoles 7-20 were afforded in better yields than those of disubstituted imidazoles 21-27. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Hsu, Mei-Yuan,Dietrich, Justin,Hulme, Christopher,Shaw, Arthur Y.
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p. 1538 - 1542
(2013/05/21)
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- Asymmetric synthesis of α-(heteroaryl)alkylamines and α-amino acids via nucleophilic 1,2-addition of lithiated heterocycles to aldehyde SAMP-hydrazones
-
The asymmetric synthesis of α-(heteroaryl)alkylamines was accomplished by employing a diastereoselective nucleophilic 1,2-addition of lithiated aromatic heterocycles to aldehyde SAMP-hydrazones, followed by BH 3·THF or SmI2 promoted removal of the chiral auxiliary. The CBz or benzoyl-protected amines were obtained in good yields (40%-78%) and excellent enantiomeric excesses (ee = 88%-99%). The methodology can be applied to the synthesis of highly enantioenriched α-amino acids (ee = 90%-99%). TUeBITAK.
- Enders, Dieter,Del Signore, Giuseppe,Raabe, Gerhard
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p. 492 - 518
(2013/08/23)
-
- Kinetic resolution of unsaturated amides in a chlorocyclization reaction: Concomitant enantiomer differentiation and face selective alkene chlorination by a single catalyst
-
The first example of a kinetic resolution via chlorofunctionalization of olefins is reported. The enantiomers of racemic unsaturated amides were found to have different hydrogen-bonding affinities for chiral Lewis bases in numerous solvents. This interaction was exploited in developing a kinetic resolution of racemic unsaturated amides via halocyclization. The same catalyst serves to both sense chirality in the substrate as well as mediate a highly face-selective chlorine delivery onto the olefin functionality, resulting in stereotriad products in up to 99:1 dr and up to 98.5:1.5 er. The selectivity factors were typically greater than 50 to allow for the simultaneous synthesis of both the products and unreacted substrates in highly enantioenriched form at yields approaching 50%. The reaction employs catalytic amounts (≤0.50 mol %) of a commercially available and recyclable organocatalyst.
- Jaganathan, Arvind,Staples, Richard J.,Borhan, Babak
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p. 14806 - 14813
(2013/10/22)
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- Fluorescent photoremovable precursor (acridin-9-ylmethyl)ester: Synthesis, photophysical, photochemical and biological applications
-
A series of carboxylic acids including amino acids were protected as their corresponding fluorescent ester conjugates by coupling with an environment sensitive fluorophore 9-methylacridine. Photophysical properties of all the ester conjugates along with the protecting group have been investigated. Interestingly, the emission properties of the ester conjugates and 9-methylacridine were found to be highly sensitive to polarity, H-bonding and pH of the environment. Photolysis of all the ester conjugates was carried out using UV light above 360 nm and it was found that in every case the corresponding carboxylic acids were released in high chemical yield. Further, intercalation and the preferred binding mode of acridine-9-methanol and its ester conjugates with DNA were studied. In vitro biological studies revealed that acridine-9-methanol has good biocompatibility, cellular uptake property and cell imaging ability. The Royal Society of Chemistry and Owner Societies 2013.
- Jana, Avijit,Saha, Biswajit,Karthik,Barman, Sharabani,Ikbal, Mohammed,Ghosh, Sudip Kumar,Pradeep Singh
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p. 1041 - 1052
(2013/09/12)
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- Direct amidation from alcohols and amines through a tandem oxidation process catalyzed by heterogeneous-polymer-incarcerated gold nanoparticles under aerobic conditions
-
We describe herein a highly elegant and suitable synthesis of amide products from alcohols and amines through a tandem oxidation process that uses molecular oxygen as a terminal oxidant. Carbon-black-stabilized polymer-incarcerated gold (PICB-Au) or gold/cobalt (PICB-Au/Co) nanoparticles were employed as an efficient heterogeneous catalyst depending on alcohol reactivity and generated only water as the major co-product of the reaction. A wide scope of substrate applicability was shown with 42 examples. The catalysts could be recovered and reused without loss of activity by using a simple operation. Gold standard: A highly efficient green method for amide synthesis from alcohols and amines catalyzed by gold nanoparticles stabilized by styrene-based copolymers has been developed (see scheme). Two catalysts have been used with high selectivity depending on the combination of substrates. These Au nanoparticle catalysts can be recovered and reused several times by simple operations. Copyright
- Soule, Jean-Francois,Miyamura, Hiroyuki,Kobayashi, Shu
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supporting information
p. 2614 - 2626
(2013/11/19)
-
- Synthesis and spectral characterization of related substances of vardenafil, an erectile dysfunction drug
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Vardenafil hydrochloride trihydrate (Levitra) is used to treat erectile dysfunction (ED) and is an inhibitor of phosphodiesterase type 5 (PDE-5) enzyme. It maintains higher levels of cyclic guanosine monophosphate (cGMP), relaxes smooth muscles, promotes penile blood flow, and enhances erectile function. During the bulk drug synthesis of vardenafil hydrochloride trihydrate, six related substances (impurities), vardenafil dimer, vardenafil N-oxide, vardenafil glycene, vardenafil oxopiperazine, vardenafil oxoacetic acid, and phenyl vardenafil were identified, and these are reported herein for the first time. The present work describes the synthesis and characterization of these impurities.
- Reddy, Vajrala Venkata,Naga Brahmeswara Rao, Mandava Venkata,Reddy, Ghanta Mahesh,Mukkanti, Khagga,Reddy, Ganta Madhusudhan
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experimental part
p. 3513 - 3523
(2012/10/18)
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- Effect of pH on the reactivity of dipeptides and α-amino acids in the N-acylation
-
The reaction kinetics of Gly, L-α-Ala, Gly-Gly, L-α-Ala-L- α-Ala and β-Ala-β-Ala with picryl benzoate in water (40 wt %)-2-propanol was investigated. At pH = 4-8 the rate constants of N-acylation of the anionic form of dipeptides are less than those of the corresponding amino acid anions, in agreement with their basicity, whereas the relative effective rate constants of reactions depend on pH: in acidic, neutral and slightly alkaline media the kef values are higher for the dipeptides, and in a strongly alkaline medium, for the amino acids. These differences are due to the changes in the concentrations of reactive forms of amino acids and dipeptides in the system at varying the medium pH.
- Kuritsyn,Kalinina,Kochetova
-
p. 1810 - 1814
(2013/06/26)
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- One-pot preparation of oxazol-5(4H)-ones from amino acids in aqueous solvents
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A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the TV-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.
- Fujita, Hikaru,Kunishima, Munetaka
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p. 907 - 912
(2012/08/08)
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- Discovery and optimization of 2-phenyloxazole derivatives as diacylglycerol acyltransferase-1 inhibitors
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In a discovery effort to find safe and effective DGAT-1 inhibitors, we have identified 2-phenyloxazole 4-carboxamide 1 as a conformationally constrained analog of a hydrazide hit, which was previously identified from high-throughput screening. Further optimization of this series has led to chemically more stable 2-phenyloxazole-based DGAT-1 inhibitor 25 with improved solubility, cell-based activity, and pharmacokinetic properties. Compound 25 also demonstrated in vivo efficacy in a diet-induced obesity (DIO) rat model.
- Yun, Weiya,Ahmad, Mushtaq,Chen, Yingsi,Gillespie, Paul,Conde-Knape, Karin,Kazmer, Sonja,Li, Shiming,Qian, Yimin,Taub, Rebecca,Wertheimer, Stanley J.,Whittard, Toni,Bolin, David
-
scheme or table
p. 7205 - 7209
(2012/01/15)
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- Powerful amide synthesis from alcohols and amines under aerobic conditions catalyzed by gold or gold/iron, -nickel or-cobalt nanoparticles
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Considering the importance of the development of powerful green catalysts and the omnipresence of amide bonds in natural and synthetic compounds, we report here on reactions between alcohols and amines for amide bond formation in which heterogeneous gold and gold/iron, -nickel, or-cobalt nanoparticles are used as catalysts and molecular oxygen is used as terminal oxidant. Two catalysts show excellent activity and selectivity, depending on the type of alcohols used. A wide variety of alcohols and amines, including aqueous ammonia and amino acids, can be used for the amide synthesis. Furthermore, the catalysts can be recovered and reused several times without loss of activity.
- Soule, Jean-Francois,Miyamura, Hiroyuki,Kobayashi, Shu
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supporting information; experimental part
p. 18550 - 18553
(2012/01/06)
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- METHODS OF TREATING OR PREVENTING PSORIASIS, AND/OR ALZHEIMER'S DISEASE USING INDANE ACETIC ACID DERIVATIVES
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The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing psoriasis and/or Alzheimer's diseases.
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Page/Page column 141
(2010/12/29)
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- Synthesis and biological activity of a series of tetrasubstituted- imidazoles as P2X7 antagonists
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A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure-activity relationships (SAR) were investigated both with respect to activity at the P2X7 receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X7 antagonist with reduced in vitro metabolism and high solubility.
- Gleave, Robert J.,Walter, Daryl S.,Beswick, Paul J.,Fonfria, Elena,Michel, Anton D.,Roman, Shilina A.,Tang, Sac-Pham
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scheme or table
p. 4951 - 4954
(2010/10/04)
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- A new method proposed for the determination of absolute configurations of α-amino acids
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Enantiopure α-amino acids were converted to 4-substituted 2-aryl- and 2-alkyl-5(4H)-oxazolones under partial racemization. These nonracemic mixtures were dissolved in CDCl3, an equimolar amount of the chiral dirhodium complex Rh2(II)[(R)-(+)-MTPA]4 (MTPA-H = Mosher's acid) was added, and the 1H NMR spectra of the resulting samples were recorded [dirhodium method). The relative intensities of 1H signals dispersed by the formation of diastereomeric adducts allow to determine the absolute configuration (AC) of the starting a-amino acids. Binding atoms in the adducts were identified by comparing the 1H and 13C chemical shifts of the oxazolones in the absence and presence of Rh2(II)[(R)-(+)- MTPA]4. Thereby, information about the scope and limits of this method can be extracted. A protocol how to use this method is presented. Copyright
- Gomez, Edison Diaz,Duddeck, Helmut
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experimental part
p. 222 - 227
(2010/02/28)
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- Brine-mediated efficient benzoylation of primary amines and amino acids
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Benzoylation of primary amines and amino acids is efficiently carried out in a brine solution using a stoichiometric amount of benzoyl chloride followed by trituration with aqueous saturated bicarbonate solution. Copyright Taylor & Francis Group, LLC.
- Chattopadhyay, Gautam,Chakraborty, Suchandra,Saha, Chandan
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experimental part
p. 4068 - 4075
(2009/04/11)
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- Organocatalytic asymmetric addition of alcohols and thiols to activated electrophiles: Efficient dynamic kinetic resolution and desymmetrization protocols
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(Chemical Equation Presented) Bifunctional urea-based cinchona alkaloid derivatives have been shown to promote highly efficient DKR reactions of azalactones using an alcohol nucleophile. The optimum catalyst is remarkably insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine-, and phenylalanine-derived azalactones to undergo DKR with unprecedented levels of enantioselectivity using a synthetic catalyst. The first DKR of these substrates by thiols and the highly enantioselective desymmetrization of a meso-glutaric anhydride by thiolysis are also reported.
- Peschiulli, Aldo,Quigley, Cormac,Tallon, Sean,Gun'ko, Yuri K.,Connon, Stephen J.
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p. 6409 - 6412
(2008/12/22)
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- Combining Magnetic Resonance Spectroscopies, Mass Spectrometry, and Molecular Dynamics: Investigation of Chiral Recognition by 2,6-di-O-Methyl-β-cyclodextrin
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EPR spectroscopy has been employed to investigate the formation of complexes between heptakis-(2,6-O-dimethyl)-β-cyclodextrin (DM-β-CD) and different enantiomeric pairs of chiral nitroxides of general structure PhCH2N(O·)CH(R)R′. Accurate equilibrium measurements of the concentrations of free and included radicals afforded the binding constant values for these nitroxides. The relationship between the stereochemistry of the DM-β-CD complexes and the thermodynamics of complexation was elucidated by correlating EPR data with 1H-1H NOE measurements carried out on the complexes between DM-β-CD and the structurally related amine precursors of nitroxides. NOE data suggested that inclusion of the stereogenic center in the DM-β-CD cavity occurs only when the R substituent linked to the chiral carbon contains an aromatic ring. For these types of complexes, molecular dynamics simulation indicated that the depth of penetration of the stereogenic center into the cyclodextrin cavity is determined by the nature of the second substituent (R′) at the asymmetric carbon and is responsible for the observed chiral selectivity. Analysis of mass spectra showed that, for the presently investigated amines, electrostatic external adducts of CDs with protonated amines are detected by ESI-MS.
- Franchi, Paola,Lucarini, Marco,Mezzina, Elisabetta,Pedulli, Gian Franco
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p. 4343 - 4354
(2007/10/03)
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- Indane acetic acid derivatives and their use as pharmaceutical agents, intermediates, and method of preparation
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This invention relates to novel indane acetic acid derivatives which are useful in the treatment of diseases such as diabetes, obesity, hyperlipidemia, and atherosclerotic diseases. The invention also relates to intermediates useful in preparation of indane acetic derivatives and to methods of preparation.
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- Novel enantioselective synthesis of both enantiomers of furan-2-yl amines and amino acids
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A new enantioselective synthesis of furan-2-yl amines and amino acids is described, in which the key step is the oxazaborolidine-catalyzed enantioselective reduction of O-benzyl (E)- and (Z)-furan-2-yl ketone oximes to the corresponding chiral amines. The chirality of the furan-2-yl amines is fully controlled by the appropriate choice of the geometrical isomer of the O-benzyl oxime. Oxidation of the furan ring furnished amino acids in high yields.
- Demir, Ayhan S.,Sesenoglu, Oezge,Uelkue, Dincer,Arici, Cengiz
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- Flow-vacuum pyrolysis of 2,5-diphenyl-4-methyloxazole
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The flow-vacuum pyrolysis of 2,5-diphenyl-4-methyloxazole (4) at 1000°C and 0.5 Torr afforded a complex reaction mixture containing: benzonitrile, diphenylmethane, 9,10-dimethylphenantrene, 9,10-dimethylantracene, fluorene, o-benzylbenzonitrile (major product, 20-22%), phenanthrene, anthracene, o,o′-dicyanodiphenyl, 9,10-anthraquinone, 2-methyl-4,5-diphenyloxazole and 1,1,2,2-tetraphenylethane. A radical- and carbene mechanism is suggested in order to rationalize the formation of the reaction products.
- Banciu, Mircea D.,Istrati, Daniela,Schiketanz, Iosif,Mihǎiescu, Dan,Drǎghici, Constantin,Malacea, Raluca
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p. 493 - 499
(2007/10/03)
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- Highly enantioselective synthesis of α,β-diaminopropanoic acid derivatives using a catalytic asymmetric hydrogenation approach
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Rh-DuPhos-catalyzed asymmetric hydrogenation of α,β-diamidoacrylates provides a highly efficient and enantioselective route to chiral α,β-diaminopropanoic acid derivatives. The mechanistic course of the hydrogenation was studied using isotopically enriched enamide complexes and phosphorus and carbon NMR. Addition of methyl α-N-benzoyl-β-N-acetyl-diaminopropenoate to the solvated catalyst gave a single 1:1 enamide complex and demonstrated the binding of the olefin and α-amide carbonyl group; the carboxylate and β-N-acyl groups did not bind to the metal. Changes to the electronic and steric properties of the β-N-acyl group were well tolerated; however, small changes to the binding α-N-acyl group were found to significantly affect hydrogenation yields.
- Robinson,Chin Yu Lim,He,Ma,Li
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p. 4141 - 4147
(2007/10/03)
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- Preparation of N-acyl derivatives of amino acids from acyl chlorides and amino acids in the presence of cationic surfactants. A variation of the Schotten-Baumann method of benzoylation of amino acids
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A very efficient method for the preparation of N-acylamino acids from the corresponding acyl chloride and amino acid is described. Amino acids, potassium carbonate, acyl chloride, and a catalytic amount of cationic surfactants were mixed in tetrahydrofuran and refluxed without ever obtaining a clear reaction mixture. After hot filtration, the product was isolated from the hot tetrahydrofuran solution in very high or almost quantitative yields.
- Jursic,Neumann
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p. 555 - 564
(2007/10/03)
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- Self-assembled organogels formed by mono-chain L-alanine derivatives
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The mono-chain L-alanine derivatives self-assemble into bilayer aggregates in a number of organic liquids and gelatinize the liquids.
- Luo,Liu,Liang
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p. 1556 - 1557
(2007/10/03)
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- Beauveria bassiana ATCC 7159 contains an L-specific α-amino acid benzamidase
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Biotransformation of a series of racemic N-benzoyl α-amino acids by the fungus Beauveria bassiana ATCC 7159 results in isolation of the corresponding D-amino acid benzamides in high enantiomeric purity and yield.
- Holland, Herbert L.,Andreana, Peter R.,Salehzadeh-Asl, Reza,Van Vliet, Aaron,Ihasz, Nancy J.,Brown, Frances M.
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p. 667 - 672
(2007/10/03)
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