- Convenient method for the synthesis of some novel chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives and biological evaluation of their antioxidant, cytotoxic, and molecular docking properties
-
Ten chiral methyl 2-(2-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)propanoate derivatives 6a-6j have been synthesized from optically pure amino methyl phenol 5 and 4-nitrophenyl chloroformate. These derivatives 6a-6j are characterized by 1H NMR, 13C NMR, FT-IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a-6j were screened for their in vitro antioxidant activity. Among the compounds 6b-d and 6h-j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e-g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT-3 (PDB ID: 1BG1) and BCL-2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of ?7.76 to ?8.41 kcal/mol, which is very close to doxorubicin (?8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
- Matam, Sivakumar,Kaliyan, Prabakaran,Selvaraj, Loganathan,Muthu, Seenivasa Perumal,Lohanathan, Bharathi Priya,Viswanadhan, Vijaya Padma,Makala, Himesh,Venkatasubramanian, Ulaganathan
-
supporting information
p. 569 - 579
(2020/12/11)
-
- A Concise Enantiodivergent Synthesis of Equol
-
Equol, a nonsteroidal estrogen produced from the metabolism of the isoflavonoid phytoestrogen daidzein, has been synthesized as both enantioenriched forms based on MacMillan's α-Arylation of carbonyl compound mediated by amino acid derived indazolidinones and copper precatalysts. The natural form of (S)-equol and its enantiomer (R)-equol have been synthesized in 8 steps from 2,4-dimethoxybenzaldehyde with good enantiomeric purity (90% ee and 90% ee, respectively).
- Uemura, Takahito,Saito, Yusuke,Sonoda, Motohiro,Tanimori, Shinji
-
p. 693 - 696
(2020/12/23)
-
- ((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-β-lactamase inhibitors: Synthesis, kinetic and crystallographic studies
-
The emergence and global spread of metallo-β-lactamase (MBL) mediated resistance to almost all β-lactam antibacterials poses a serious threat to public health. Since no clinically useful MBL inhibitors have been reported, there is an urgent need to develop new potent broad-spectrum MBL inhibitors effective against antibacterial resistance. Herein, we synthesized a set of 2-substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of which displayed potent inhibition with high ligand efficiency to the clinically relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc chelators in solution, and they bind reversibly to VIM-2 but dissociate very slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating the active site zinc ions and interacting with catalytically important residues. Further cell- and zebrafish-based assays revealed that the inhibitors slightly increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they have no apparent toxicity to the viability of HEK293T cells and the zebrafish embryogenesis.
- Liu, Sha,Jing, Li,Yu, Zhu-Jun,Wu, Chengyong,Zheng, Yongxiang,Zhang, En,Chen, Qiang,Yu, Yamei,Guo, Li,Wu, Yong,Li, Guo-Bo
-
p. 649 - 660
(2018/02/10)
-
- Synthesis of novel 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-ones and 1,2,4-triazin-6(5H)-ones from optically active α-aminocarboxylic acid hydrazides
-
New derivatives of 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-one and 1,2,4-triazin-6(5H)-one were synthesized via reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The factors influencing the formation of the unexpected five-membered products and attempts to elucidate the mechanism are discussed.
- Kudelko, Agnieszka,Zieliński, Wojciech,Jasiak, Karolina
-
supporting information
p. 4637 - 4640
(2013/08/23)
-
- The reaction of optically active α-aminocarboxylic acid hydrazides with triethyl orthoesters
-
New derivatives of 2-(1-amino-1-phenylmethyl)-1,3,4-oxadiazole and 1,2,4-triazin-6-one were synthesised in the reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The electronic and steric effects of substituents at the α position influencing the formation of five- or six-membered products are discussed.
- Kudelko, Agnieszka,Zieliński, Wojciech,Ejsmont, Krzysztof
-
experimental part
p. 7838 - 7845
(2011/10/12)
-
- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
-
The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
- -
-
Page/Page column 45-49; 64
(2010/12/31)
-
- New phenylglycine-derived primary amine organocatalysts for the preparation of optically active warfarin
-
In this work we present new, fully synthetic phenylglycinederived primary amine organocatalysts useful, for the onestep preparation, of optically active warfarin, an. important anticoagulant. Both enantiomeric forms of the catalysts are equally available and can be prepared by robust procedures without recourse to chromatographic purification. Together with a co-catalyst, particularly acetic acid or2,4-dinitrophen- ol, they can furnish warfarin in approximately 80 % ee and represent inexpensive alternatives to other primary amine organocatalysts such as the chiral diamines and. Cinchona-derived primary amines.
- Kristensen, Tor E.,Vestli, Kristian,Hansen, Finn K.,Hansen, Tore
-
experimental part
p. 5185 - 5191
(2010/01/11)
-
- An efficient synthesis of new 2-aminomethyl-1,3,4-oxadiazoles from enantiomeric phenylglycine hydrazides
-
New derivatives of 2-aminomethyl-1,3,4-oxadiazole were synthesized in the reactions of N-protected phenylglycine hydrazides and triethyl orthoesters (orthoformate, orthoacetate, orthopropionate, orthobenzoate) in the presence of glacial acetic acid. Studies on the cleavage reactions of the acid-sensitive N-BOC and N-Ac 1,3,4-oxadiazoles are presented. Spectral characteristics of the compounds and attempts to elucidate the racemization phenomenon observed in products are also discussed.
- Kudelko, Agnieszka,Zieliński, Wojciech
-
experimental part
p. 1200 - 1206
(2009/04/10)
-
- Emergence of a single solid chiral state from a nearly racemic amino acid derivative
-
The evolution of a single chiral solid state is reported for an amino acid derivative starting from a nearly racemic mixture of solid left- and right-handed crystals. Attrition-enhanced dissolution and recrystallization processes based on solubility considerations of the Gibbs-Thomson rule, coupled with solution-phase racemization, drive this near-equilibrium system inexorably to single chirality in the solid phase. Copyright
- Noorduin, Wim L.,Izumi, Toshiko,Millemaggi, Alessia,Leeman, Michel,Meekes, Hugo,Van Enckevort, Willem J. P.,Kellogg, Richard M.,Kaptein, Bernard,Vlieg, Elias,Blackmond, Donna G.
-
p. 1158 - 1159
(2008/09/20)
-
- Asymmetric synthesis of protected arylglycines by rhodium-catalyzed addition of arylboronic acids to N-tert-butanesulfinyl imino esters
-
A new method for the Rh(I)-catalyzed addition of arylboronic acids to N-tert-butanesulfinyl imino esters has been developed for the asymmetric synthesis of arylglycine derivatives. This method provides high yields (61-90%) and diastereoselectivities (>98:2) for a variety of functionalized arylboronic acids. The N-sulfinyl arylglycine ester products are versatile intermediates for further transformations, including selective protecting group removal, conversion to β-amino alcohols, and direct incorporation into peptides. Copyright
- Beenen, Melissa A.,Weix, Daniel J.,Ellman, Jonathan A.
-
p. 6304 - 6305
(2007/10/03)
-
- Practical synthesis of fluorous oxazolidinone chiral auxiliaries from α-amino acids
-
A series of new fluorous-supported oxazolidinone chiral auxiliaries has been prepared using a versatile and general five-step pathway, starting from readily available chiral α-amino acids. The key feature of this synthesis is the efficient generation of a suitably active perfluoroalkyllithium species. By use of this protocol, the auxiliaries can be obtained in high enantiomeric purity and on multigram scales from L-phenylalanine and L-valine with overall yields as high as 55%. The new methodology also incorporates fluorous solid-phase extraction on the large scale, allowing bulk quantities (up to 25 g) of fluorous compounds to be purified from the crude reaction mixture.
- Hein, Jason E.,Geary, Laina M.,Jaworski, Ashley A.,Hultin, Philip G.
-
p. 9940 - 9946
(2007/10/03)
-
- The 'SuperQuat' (R)-4-phenyl-5,5-dimethyl oxazolidin-2-one as an effective chiral auxiliary for conjugate additions: Asymmetric synthesis of (-)-aplysillamide B.
-
(R)-4-Phenyl-5,5-dimethyl-oxazolidin-2-one, readily available from D- phenylglycine, is shown to be an effective chiral auxiliary for stereoselective conjugate additions to attached α,β-unsaturated N-acyl moieties. Its utility is demonstrated by the asymmetric synthesis of the antifungal, antibacterial (-)-Aplysillamide B.
- Davies, Stephen G.,Sanganee, Hitesh J.,Szolcsanyi, Peter
-
p. 3337 - 3354
(2007/10/03)
-
- Asymmetric alkylations using SuperQuat auxiliaries - An investigation into the synthesis and stability of enolates derived from 5,5-disubstituted oxazolidin-2-ones
-
Studies on the alkylation of enolates derived from a range of N-acyl-5,5-dimethyloxazolidin-2-ones and N-acyl-5,5-diphenyloxazolidin-2-ones reveal that high yields and high diastereoselectivities are best obtained when homochiral 4-isopropyl-5,5-dimethyloxazolidin-2-one is employed as a chiral auxiliary.
- Bull, Steven D.,Davies, Stephen G.,Jones, Simon,Sanganee, Hitesh J.
-
p. 387 - 398
(2007/10/03)
-
- Synthesis and structure determination of novel chiral imine-alkoxytitanium complexes
-
The imines 4 containing a diphenylcarbinol moiety serve as chiral ligands in novel enantiomerically pure imine-alkoxytitanium(IV) complexes. Depending on the molar ratio of the starting materials, imines 4 and titanium tetraisopropoxide, mono-chelated complexes 5 or bis-chelated complexes 6/7 result. The latter are formed diastereoselectively and the isomers 6 are main or exclusive products. Their (A) configuration is determined by a crystal-structure analysis of 6b. The bis-ligand complexes 6 or mixtures of 6/7, which are found to be remarkably stable, are used as precursors not only for the reactive dihalo complexes 8a/8b but also for the preparation of the mixed chloroisopropoxytitanium complex 8c.
- Fleischer, Ralf,Wunderlich, Hartmut,Braun, Manfred
-
p. 1063 - 1070
(2007/10/03)
-
- Synthesis of α-phenyl-1-(R)-(-)-piperidineacetic esters
-
Several α-phenyl-1-(R)-(-)-piperidineacetic esters 3(a-e), were obtained in pure enantiomeric form by condensing (R)-(-)-α-phenylglycine esters 2(a-e) with 1,5-dibromopentane. Similarly, (R)-(-)-α-phenylglycine esters, 2(a-e), were prepared from (R)-(-)-α-phenylglycine 1 with high yields.
- Juarez, Jorge,Gnecco, Dino,Galindo, Alberto,Enriquez, Raul G.,Marazano, Christian,Reynolds, William F.
-
p. 203 - 206
(2007/10/03)
-
- On the mechanism of the Fe(CO)5-catalyzed Kharasch reaction 1. Stereochemistry of addition of BrCCl3 to (R)-3-(E)-cinnamoyl-4-phenyloxazolidin-2-one, (R)-3-(E)-acryloyl-4-phenyloxazolidin-2-one, and their π-complexes with Fe(CO)4
-
Regioselectivity and diastereoselectivity of the addition of BrCCl3 to (R)-3-(E)-cinnamoyl-4-phenyloxazolidin-2-one (1) and (R)-3-(E)-acryloyl-4-phenyloxazolidin-2-one (2) catalyzed by Fe(CO)5 or initiated with benzoyl peroxide were investigated. Stereochemistry of the reaction of BrCCl3 with the π-complexes (4R,αS,βS)-η 2-(3-(E)-cinnamoyl-4-phenyl-oxazolidin-2-one)irontetracarbonyl (3a) and (4R,αR)-η 2-(3-acryloyl-4-phenyloxazolidin-2-one)irontetracarbonyl (4b) was also studied. The results obtained allow the following conclusions to be drawn: (1) the thermal Kharasch reaction catalyzed by Fe(CO)5 proceeds by a redox catalysis mechanism; (2) iron (in any of its oxidation states) is not coordinated to olefins in the transition state of the reaction; (3) the transfer of the halogen atom on the radical adduct probably occurs inside a radical-iron cation pair.
- Tararov,Savel'eva,Struchkov,Pisarevskii,Raevskii,Belokon'
-
p. 600 - 609
(2007/10/03)
-
- A convenient synthesis of optically active phenylglycine
-
Optically active R phenylglycine methyl ester hydrochloride (ee = 98%) was prepared in 90% yield from racemic phenylglycine. The key step was the base catalysed diastereoselective addition at -78°C of R pantolactone to the N-phthalyl protected phenylglycine ketene.
- Calmes, Monique,Daunis, Jacques,Mai, Nathalie,Natt, Francois
-
p. 379 - 380
(2007/10/03)
-
- New Chiral Anisotropic Reagents for Determining the Absilute Configuration of Carboxylic Acids
-
Enantiomers of phenylglycine dimethylamide (PGDA) and phenylglycine methyl ester (PGME) were prepared as the reagents for determining the absolute configuration of carboxyl acids of type I.Each enantiomer of PGDA and PGMA was condensed with several carbixylic acids, the absolute configuration of which is known.The absolute configuration of the carboxylic acids, predicted by Δδ values (Δδ = δS - δR) of the protons and Model B, is the same as the known one without exception.
- Nagai, Yuriko,Kusumi, Takenori
-
p. 1853 - 1856
(2007/10/02)
-
- A simple and efficient procedure for the preparation of chiral 2-oxazolidinones from α-amino acids
-
A modified procedure for the title transformation is described which avoids: (i) a potentially hazardous borane reduction step, and (ii) the intermediacy of water soluble amino alcohols.
- Lewis,McKillop,Taylor,Watson
-
p. 561 - 568
(2007/10/02)
-
- Influence of a Hydroalcoholic Solvent on the Enantioselectivity of α-Amino nitrile Hydration Catalysed by Chiral Ketones
-
The enantioselective hydration of α-aminonitriles 1, RCH(CN)NH2 i; 1c: R = Ph> has been achieved in an alkaline hydroalcoholic medium in the presence of chiral ketonic catalysts.Of the different ketones used, (-)-(5R,3R,2R)-5-(methylethenyl)-3-cyano-2-methylcyclohexanone (8) gives rise to significant enantioselectivity D/kL = 2.1; T = 10 deg C; solvent, water-propan-2-ol (45:55,v/v)>.Although the structure of the catalyst could probably be improved, we show in this paper that the efficiency and especiallythe enantioselectivity of the catalyst are not only under steric control but also depend on the nature and composition of the hydroalcoholic solvent.Thus, for the three aminonitriles studied in the presence of the catalyst 8, the increase in percentage of propan-2-ol favours the hydration of the D α-aminonitrile as shown for the hydration of 1c for which the ratio kD/kL increases threefold when the percentage of propan-2-ol increases from 10 to 95percent.
- Lagriffoul, Pierre-Henri,Tadros, Ziad,Taillades, Jacques,Commeyras, Auguste
-
p. 1279 - 1285
(2007/10/02)
-
- HETEROCYCLES FROM NITRILE IMINES. PART IV. CHIRAL 4,5-DIHYDRO-1,2,4-TRIAZIN-6-ONES
-
The reaction of nitrile imines (II) with α-amino esters (III) proceeds with no detectable racemization and constitutes a convenient synthetic route to 4,5-dihydro-1,2,4-triazin-6-ones (IV).Permangamate oxidation of heterocycles (IV) affords the corresponding 1,2,4-triazin-6-ones (V).The reaction of (II) with β-amino esters gives the respective acyclic amidrazone adducts (VI).
- El-Abadelah, Mustafa M.,Hussein, Ahmad Q.,Thaher, Bassam A.
-
p. 1879 - 1895
(2007/10/02)
-
- ENANTIOSELECTIVE ELECTROPHILIC BOND CONSTRUCTION TO THE α-CARBON OF α-AMINOACIDS
-
In this report, we describe three possibilities for aminoacid synthesis using an enantioselective electrophilic process.Thus, enantioselective carboxylation, alkylation and protonation of Schiff bases yield optically active aminoacids with e.e. up to 76percent.
- Duhamel, Lucette,Duhamel, Pierre,Fouquay, Stephane,Eddine, Jamal Jamal,Peschard, Olivier,et al.
-
p. 5495 - 5506
(2007/10/02)
-
- AN EFFICIENT SYNTHESIS OF N-HYDROXY-α-AMINO ACID DERIVATIVES OF HIGH OPTICAL PURITY.
-
Conversion of α-hydroxy esters via triflates into compounds 3 proceeds in chemical yields ranging from 78 to 89percent and with optical purities ranging from 76 to 100percent.
- Feenstra, R. W.,Stokkingreef, E. H. M.,Nivard, R. J. F.,Ottenheijm, H. C. J.
-
p. 1215 - 1218
(2007/10/02)
-
- SYNTHESE D'AMINOPHOSPHINEPHOSPHINITES CHIRAUX. UTILISATION EN REDUCTION ASYMETRIQUE CATALYTIQUE
-
The chiral aminophosphinephosphinites ligands (AMPP) are directly synthesized from natural amino alcohols or by reduction of formyl esters of α-amino acids and PPh2Cl. Their cationic rhodium complexes have been found to be excellent catalysts for enantioselective hydrogenation of dehydroamino acids (ee ca. 86percent, yield ca. 100percent) for example.Asymmetric reduction of ketones can also be performed with the new alkyl AMPP* modified rhodium catalyst (ee 50percent).
- Karim, A.,Mortreux, A.,Petit, F.,Buono, G.,Pfeiffer, G.,Siv, C.
-
-
- The direct chemical conversion of peptides to β-lactams
-
Appropriately protected seryldipeptides which have a relatively acidic proton (H1 of 1) on the α' C can be efficiently converted to β-lactams by reaction with azodicarboxylates and triphenylphosphine. Application of the same reaction conditions to serylamides which lack an acidic α' proton provided dehydropeptides as the major product. Model reactions and potential intermediates which rationalize these results are described.
- Miller,Mattingly
-
p. 2563 - 2570
(2007/10/02)
-
- Interproton Coupling over Five Bonds 5J(H-Cα-C(O)-N-Cα-H) in the Peptide Moiety: The Importance of Specific Association Effects
-
An experimental and theoretical study is presented of the conformational and solvent dependencies of long-range H-H coupling constants 5J(H-Cα-C(O)-N-Cα-H) in compounds which model the peptide backbone.Molecular orbital results for Fermi contact coupling in cis- and trans-N-methylacetamides do not follow a conformational dependence of the homoallylic type; negative values are predicted for most out-of-plane orientations of the Cα-H bonds.In addition, the calculated values for 5CcisHH' and 5CtransHH' are of opposite signs in the planar conformation of cyclo-(Gly-Gly) and the boat conformation of cyclo-(Gly-Tyr).However, relative sign measurements show that these two coupling constants are of the same sign in cyclo-(Gly-Tyr), and that both are positive in cyclo-(Gly-Phgly).The inclusion of five water molecules in the MO calculations for cis-N-methylacetamide and ten water molecules in association with cyclo-(Gly-Gly) led to both positive 5JcisHH' and 5JtransHH'.As a consequence, any applicability of the empirical relationship of 5J(H-Cα-C(O-N-Cα-H) to φ and ψ angles in peptides does not have any theoretical basis in the molecular orbital theory for unhydrated amide bonds.
- Barfield, M.,Al-Obeidi, F.A.,Hruby, V.J.,Walter, S.R.
-
p. 3302 - 3306
(2007/10/02)
-
- Derecemization par protonation enantioselective. Application a un α-aminoacide, la phenylglycine
-
This work describes the application of deracemization by enantioselective protonation to α-aminoacid derivatives.Esters of phenylglycine are readly converted into Schiff bases.Melanation of the latter by a lithium amide, followed by protonation by a chiral acid, leads to the optically active starting materials (e.e. as high as 70percent).Chiral acids can easily be retrieved after protonation with excellent yields and conservation of enantiomeric purity.A mechanism responsible for the asymmetric induction is suggested by means of a study of the parameters modifying the selectivity, such as the nature of protecting groups, chiral acid, and lithium amide.
- Duhamel, Lucette,Plaquevent, Jean-Christophe
-
-
- Deracemization by enantioselective protonation IV an improved method for the enantiomeric enrichment of α-aminoacids using metalation by means of chiral amides
-
Optically active α-aminoesters are obtained by metalation of the corresponding Schiff bases by chiral lithium amide followed by protonation by an achiral or a chiral acid. 70 % e.e. can be obtained.
- Duhamel, Lucette,Plaquevent, Jean-Christophe
-
p. 2521 - 2524
(2007/10/02)
-