- Preparation and reactions of certain racemic and optically active cyanohydrins derived from 2-chlorobenzaldehyde, 4-fluorobenzaldehyde, benzo[d][1,3]-dioxole-5-carbaldehyde and 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. Antimicrobial and in vitro antitumor evaluation of the products
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THE CHEMOENZYMATIC reaction of selected aldehydes, namely 2-chlorobenzaldehyde (1a), 4-fluorobenzaldehyde (1b), benzo[d][1,3]dioxole-5-carbaldehyde (1c) and/or 2,3-dihydrobenzo [b] [1,4] dioxine-6-carbaldehyde (1d) with hydrogen cyanide in presence of (R)-oxynitrilase (R)-Pa HNL [EC 4.1.2.10] from almonds, as a chiral catalyst, gave the optically active cyanohydrin enantiomers ( R)-2a-c, respectively. Acetone cyanohydrin (3), was also used, as a transcyanating agent, to give the same products. The racemic cyanohydrins (R,S)-2a-d have been synthesized, as well, by treating compounds 1a-d with aqueous potassium cyanide solution in presence of a saturated solution of sodium metabisulphite (Na2S2O5). The optical purity of cyanohydrins (R)-2a-c was determined through their derivatization with (S)-naproxen chloride (S)-5 to the respective diastereomers (R,2S)-6a-c which were obtained in diastereomeric excess (de) values up to 93 % (1H NMR). Heating compounds (R)-2a,b and / or their racemic analogues (R,S)-2a-c with concentrated hydrochloric acid gave the respective α-hydroxycarboxylic acids 7a-c. Moreover, reduction of cyanohydrins (R,S)-2b,c under different conditions resulted in a hydrodecyanation giving the respective primary alcohols 8a,b. Structures and configurations of the new compounds were confirmed with compatible elementary microanalyses and spectroscopic (IR, 1H NMR, 13C NMR, MS and single crystal X-ray crystallography) measurements. The antimicrobial activity of derivatives 6a-d against four bacterial species (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and two fungi (Aspergillus flavus and Candida albicans) were undertaken. Moreover, compounds (R,2S)-6b, (R,2S)(S,2S)-6b and (R,2S)-6c were screened for their in virto antitumor activity against three human solid cancer cell lines (HCT 116, HepG2 and MCF-7). In general, the tested compounds were found inactive or showed weak activities in comparison with the standard drugs.
- Yosef, Hisham Abdallah A.,Elmasry,Ibrahim, Nabila M.,Ismael, Eman H. I.,Mahran
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p. 301 - 328
(2017/06/08)
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- The Synthesis of Chiral α-Aryl α-Hydroxy Carboxylic Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation
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A ruthenocenyl phosphino-oxazoline-ruthenium complex (RuPHOX?Ru) catalyzed asymmetric hydrogenation of α-aryl keto acids has been successfully developed, affording the corresponding chiral α-aryl α-hydroxy carboxylic acids in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 5000 S/C) and the resulting products can be transformed to several chiral building blocks, biologically active compounds and chiral drugs. (Figure presented.).
- Guo, Huan,Li, Jing,Liu, Delong,Zhang, Wanbin
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p. 3665 - 3673
(2017/09/11)
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- Solid phase behavior in the chiral systems of various 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives
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The solid phase behavior of a series of monosubstituted F-, Cl-, Br-, I-, and CH3- and two 2,4-halogen-disubstituted 2-hydroxy-2-phenylacetic acid (mandelic acid) derivatives was investigated. The study includes detailed information about melting temperature, melting enthalpy, X-ray diffraction data, as well as selected binary phase diagrams of the respective chiral systems. Aside from the known metastable conglomerate 2-chloromandelic acid, evidence for two more metastable conglomerates was found.
- Von Langermann, Jan,Temmel, Erik,Seidel-Morgenstern, Andreas,Lorenz, Heike
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p. 721 - 728
(2015/03/30)
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- Kinetic resolution of mandelate esters via stereoselective acylation catalyzed by lipase PS-30
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By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.
- Chen, Peiran,Yang, Wenhong
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supporting information
p. 2290 - 2294
(2014/04/17)
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- Relationships between the racemic structures of substituted mandelic acids containing 8- and 10-membered hydrogen bonded dimer rings
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The structures of 27 monosubstituted mandelic acids, including several of their polymorphs, plus unsubstituted mandelic acid itself (two polymorphs) are investigated for structural similarity. The results, presented pictorially as a structural relationship plot, show that rather more structures are built up from the carboxyl-chain hydroxyl hydrogen bonded dimer than from the conventional carboxylic acid dimer. The results show how all the structures are related and, based on the two types of dimer, the degree of similarity that they possess. Some structures with Z′ > 1 contain both sorts of dimers and there are many examples of isostructural sets within the structures so far determined. We also present an example where analysing similarity in related families of structures highlights a structure that should be present and which has indeed then proceeded to be synthesised and determined.
- Coles,Ellis,Leung,Sarson,Threlfall,Tizzard
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p. 10816 - 10823
(2015/02/19)
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- Carboxylation with CO2 via brook rearrangement: Preparation of α-hydroxy acid derivatives
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In the presence of CsF, a wide range of α-substituted α-siloxy silanes were carboxylated under a CO2 atmosphere (1 atm) via Brook rearrangement. A variety of α-substituents including aryl, alkenyl, and alkyl groups were tolerated to afford α-hydroxy acids in moderate-to-high yields. One-pot synthesis from aldehydes using PhMe2SiLi and CO 2 was also possible, providing α-hydroxy acids without the isolation of an α-hydroxy silane.
- Mita, Tsuyoshi,Higuchi, Yuki,Sato, Yoshihiro
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- Structures of Racemic Monofluoro-Substituted Mandelic Acids, Their Relation to the Thermochemical Properties and an Analysis of Short Intermolecular Fluorine-Carbon Contacts
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The structures of the three monofluoro-substituted mandelic acids (C8H7FO3, Mr=170.14) have been determined from low-temperature X-ray diffraction data . o-Fluoromandelic acid, monoclinic, P21/c, a=8.4238 (12), b=5.4766 (7), c=15.959 (2) Angstroem, β=95.962 (11)o, V=732.3 (3) Angstroem3, Z=4, Dx=1.543 g cm-3, μ=11.25 cm-1, F(000)=352, R=0.040 for 1357 contributing reflections, m.p. 388.3 (5) K. m-Fluoromandelic acid (metastable modification), monoclinic, P21/a, a=10.8657 (14), b=9.2663 (10), c=15.722 (2) Angstroem, β=107.474 (10)o, V=1509.9 (6) Angstroem3, Z=8, Dx=1.497 g cm-3, μ=10.92 cm-1, F(000)=704, R=0.048 for 2977 contributing reflections, m.p. 368.4 (5) K. p-Fluoromandelic acid, orthorhombic, Pbca, a=9.4685 (9), b=16.497 (2), c=9.7677 (8) Angstroem, V=1525.7 (5) Angstroem3, Z=8, Dx=1.481 g cm-3, μ=10.80 cm-1, F(000)=704, R=0.042 for 1489 contributing reflections, m.p. 408.9 (5) K.The results obtained from the structure determination are related to their physico-chemical properties examined by differential scanning calorimetry (DSC).The DSC measurements showed that m-fluoromandelic acid is prepared as a metastable modification.The distortions of the angles of the benzene rings observed in the three acids are identical, within experimental error, to those predicted from the sum of the substituent effects.Hydrogen bonds are important for the crystal packing in all these structures, and in addition very short distances are observed in the ortho- and para-substituted acids between the F atom and the C atom of the carboxylic acid group.Semi-empirical calculations indicated that these short distances correspond to attractive electrostatic interactions.The carbon-fluorine interactions were also elucidated by a search in the Cambridge Structural Database. m-Fluoromandelic acid has the lowest melting enthalpy and entropy.This is consistent with the lack of C...F interactions and the presence of two molecules per asymmetric unit in this compound.The ortho and para acids which have similar intermolecular interactions have similar melting enthalpies and entropies, which are higher than those observed in m-fluoromandelic acid.
- Larsen, Sine,Marthi, Katalin
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p. 373 - 381
(2007/10/02)
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- Reduction of manganate(VI) by mandelic acid and its significance to development of a general mechanism for oxidation of organic compounds by high-valent transition metal oxides
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Results obtained from a study of the oxidation of mandelic acid and cyclobutanol by manganate(VI) indicate that reaction mechanisms traditionally applied to oxidations of this type (i.e., hydrogen atom or hydride ion transfers) may not be correct. Instead it appears that the reaction may be initiated by a 2 + 2 addition of the α-C-H bond to a manganese oxo double bond. This interpretation may be useful in the development of a general mechanism for the oxidation of organic compounds by high-valent transition metal oxides including more common oxidants such as permanganate, ruthenium tetroxide, and chromic acid.
- Lee, Donald G.,Chen, Tao
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p. 11231 - 11236
(2007/10/02)
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- The Oxidation of Alcohols by Permanganate. A Comparison with Other High-Valent Transition-Metal Oxidants
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The results obtained from a study of the oxidation of mandelic acid and cyclobutanol by permanganate in 1.0 M KOH are best accomodated by a mechanism in which the initial reaction is the addition of a manganese-oxo bond to the α-C-H bond of the alcohol, followed by homolytic cleavage of the resulting Mn-C bond to give free-radical intermediates.A comparison with other high-valent transition-metal oxidants suggests that it is possible to systematically classify the way in which these reagents react with alcohols on the basis of the initial reaction (C-H or O-H addition) and the cleavage mode of the metal-oxygen or metal-carbon bond (homolytic or heterolytic).The approach provides a framework for understanding these reactions that is less chaotic than the current situation where distinctive mechanisms have been proposed for each individual oxidant.
- Lee, Donald G.,Chen, Tao
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p. 5341 - 5345
(2007/10/02)
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- N-(1-ARYL-2,2,2-TRIHALOGENOETHYL)CARBOXAMIDES
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The readily obtained products from the condensation of trihalogenoacetaldehydes with carboxamides react with benzene and its homologs in the presence of concentrated sulfuric acid with the formation of N-(1-aryl-2,2,2-trihalogenoethyl)carboxamides.The latter were used for the production of 1-aryl-2,2,2-trihalogenoethylamines and 1-acylimino-1-aryl-2,2,2-trihalogenoethanes.
- Bal'on, Ya. G.,Smirnov, V. A.
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p. 2051 - 2054
(2007/10/02)
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- SYNTHESIS AND SOME PROPERTIES OF 1,1-DI(ALKOXYCARBONYLAMINO)-2,2-DIHALOGENO- AND 1,1-DI(ALKOXYCARBONYLAMINO)-2,2,2-TRIHALOGENOETHANES
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1,1-Di(alkoxycarbonylamino)-2,2,2-trihalogenoethanes were obtained by heating trihalogenoacetaldehydes or their hydrates with urethanes in a ratio of 1:2 in the presence of catalytic amounts of concentrated sulfuric acid.The products were reduced selectively with aluminum amalgam in 90percent alcohol to 1,1-di(alkoxycarbonylamino)-2,2-dihalogenoethanes.Compounds of both types react smoothly with benzene and its homologs in the presence of concentrated sulfuric acid and give 1-alkoxycarbonylamino-1-aryl-2,2-dihalogeno- and 1-alkoxycarbonylamino-1-aryl-2,2,2-trihalogenoethanes respectively.In an alkaline medium the latter are cleaved to aryloxyacetic acid, and with phosphorus pentachloride they form 1-aryl-2,2-dihalogeno- and 1-aryl-2,2,2-trihalogenoethyl isocyanates.
- Bal'on, Ya. G.,Smirnov, V. A.
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p. 2249 - 2254
(2007/10/02)
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- pKa values for substituted acetophenones: values determined by study of rates of halogenation
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pKa values in aqueous solution have been determined for seven p-substituted acetophenones.The determinations are based on the diffusion-controlled reaction of an enolate with hypochlorous acid.The values determined for the acetophenones are as follows: substituent, value; H, 18.4; p-MeO, 19.0; p-F, 18.5; p-Cl, 18.1; p-Br, 18.0; p-NO2, 16.7; p-Me3N+, 17.1. ρ for these pKa values is -1.95.Using literature values for the enol content we show that most of this ρ value reflects substituent effects upon enolization.With relatively high hydroxide and low hypochlorite concentrations the major products from chlorination of acetophenones are the corresponding mandelic acids.Under similar conditions bromination of acetophenone gives benzoic acid.
- Guthrie, J. Peter,Cossar, John,Klym, Alex
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p. 2154 - 2159
(2007/10/02)
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- 7-α-Amino-substituted acylamino-3-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acids
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Certain 7-acylamido-3-(1-carboxy-loweralkyl-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acids and their salts and easily hydrolyzed esters of the 4-carboxyl group were synthesized and found to be potent antibacterial agents which exhibited good aqueous solubility. In a preferred embodiment the 7-substituent was 2'-aminomethylphenylacetamido.
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- 7-(D-α-Hydroxy-2-arylacetamido)-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo-[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids and derivatives
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7-(D-α-Hydroxy-2-arylacetamido)-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids and derivatives containing blocking groups on the α-hydroxy group and their nontoxic, pharmaceutically acceptable salts are valuable as antibacterial agents and are particularly valuable as therapeutic agents in poultry and in animals, including man, in the treatment of infectious diseases caused by many Gram-positive and Gram-negative bacteria. A preferred compound is 7-(D-mandelamido)-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acid.
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- 7-(D-α-Hydroxy-2-arylacetamido)-3-(tetrazolo-[4,5-b]pyridazin-6-ylthiomethyl)-3-cephem-4-carboxylic acids
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7-(D-α-Hydroxy-2-arylacetamido)-3-(tetrazolo-[4,5-b]pyridazin-6-ylthiomethyl)-3-cephem-4-carboxylic acids and their nontoxic, pharmaceutically acceptable salts are valuable as antibacterial agents and are particularly valuable as therapeutic agents in poultry and animals, including man, in the treatment of infectious diseases caused by many Gram-positive and Gram-negative bacteria.
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