(Hydroxyimino)Phosphonoacetic Acids: Synthesis,Stereochemistry and Reactivity

Abstract

Individual E/Z isomers of the C-methyl ester 1 of α-(hydroxyimino)phosphonoacetic acid (“troika acid”) were recently prepared as dicyclohexylammonium salts and found to be stable at neutral pH.¹ On alkaline demethylation followed by pH adjustment to 6–7, E?1 and Z?1 stereospecifically undergo P-C_αand C_α-C_β cleavage, respectively.¹ Herein we report synthesis of the corresponding P-methyl ester from trimethyl phos-phonoacetate 2. The product was isolated as its bis-DCHA⁺ salt E-3, with stereochemistry assigned by NMR.²     

(Trifluoromethoxy)Phenylboronic Acids: Structures,Properties, and Antibacterial Activity

Three isomers of (trifluoromethoxy)phenylboronic acids were studied in the context of their physicochemical, structural, antimicrobial and spectroscopic properties. They were characterized by ¹H, ¹³C, ¹¹B and ¹⁹F NMR spectroscopy. The acidity of all the isomers was evaluated by both spectrophotometric and potentiometric titrations. The introduction of the -OCF₃ group influences the acidity, depending, however, on the position of a substituent, with the ortho isomer being the least acidic. Molecular and crystal structures of ortho and para isomers were determined by the single crystal XRD method. Hydrogen bonded dimers are the basic structural motives of the investigated molecules in the solid state. In the case of the ortho isomer, intramolecular hydrogen bond with the -OCF₃ group is additionally formed, weaker, however, than that in the analogous -OCH₃ derivative, which has been determined by both X-Ray measurements as well as theoretical DFT calculations. Docking studies showed possible interactions of the investigated compounds with LeuRS of Escherichia coli. Finally, the antibacterial potency of studied boronic acids in vitro were evaluated against Escherichia coli and Bacillus cereus.     

Enantioselective Synthesis of (1R,2S) and (1S,2S) Dehydrocoronamic Acids

Thanks to the successive use of two esterases with different regioselectivities and conventional organic chemistry we have synthesized (1R,2S) and (1S,2S) dehydrocoronamic acids.     

Solution Equilibria of Ternary Systems Involving Nickel(II) Ion,Picolinic Acid,and the Amino Acids Histidine,Cysteine, Aspartic and Glutamic Acids

Solution equilibria of the ternary systems Ni(II)–picolinic acid (Hpic) and the amino acids aspartic acid (H₂asp), glutamic acid (H₂glu), cysteine (H₂cys) and histidine (Hhis), where the amino acids are denoted as H _i L, have been studied pH-metrically. The formation constants of the resulting mixed ligand complexes have been determined at 25 °C using a ionic strength 1.0 mol·dm^?3 NaCl. In the Ni(II)–Hpic–H₂asp and Ni(II)–Hpic–H₂glu systems, the complexes [Ni(pic)H₂L]⁺, Ni(pic)HL, [Ni(pic)L]^? and [Ni(pic)L(OH)]^2? were detected. In the Ni(II)–Hpic–H₂cys system the complexes [Ni(pic)H₂L]⁺ and [Ni(pic)L]^? are present. Additionally, in the Ni(II)–Hpic–Hhis system the species [Ni(Hpic)HL]²⁺, Ni(pic)L and [Ni(pic)L(OH)]^? were identified. The species distribution diagrams as functions of pH are briefly discussed.     

Synthesis,Characterization,Biological and Docking Simulations of 4-(Benzylideneamino) Benzoic Acids

The present research paper presents the synthesis, characterization, biological and computational studies of 4-(benzylideneamino) benzoic acid derivatives(3a~3g). Derivatives 3a~3c displayed best antidiabetic potential with a glucose-lowering effect compared to the reference drug Glibenclamide. Biochemical parameters including plasma glucose, serum triglycerides, cholesterol, alanine amino transferase and aspartate amino transferase levels showed significant alterations in concentrations relative to the control. Similarly, the derivatives 3a, 3d and 3e displayed potent in vitro antibacterial potential. Molecular docking simulations delineated that the ligands and complexes were stabilized at the active site by electrostatic and hydrophobic forces, consistent with the corresponding experimental results. In silico study of the binding pattern predicted that the synthesized ligands, 3d and 3a could serve as a potential surrogate for hit-to-lead generation and the design of novel antibacterial drugs.     

Tetronic Acids and Derivatives Part VIII (1) o-Alkylation of 3-Unsubstituted Tetronic Acids

4-methoxy-(5H)-furan-2-ones 1 are useful starting materials for the synthesis of naturally occuring lactones². In a previous communication we have described an efficient entry to 4-alkoxy-(5H)-furan-2-ones 1–3 (alkyl tetronates) by lactonization of ethyl 4-acetoxy 3-ketoesters 4 using hydrochloric acid in several alcohols¹. The detection of 4-hydroxy-(5H)-furan-2-ones 5 (tetronic acids) during the reaction course³ allowed us to postulate them as intermediates which were subsequently etherified to the products 1–3. In a very recent communication⁴, it was claimed that attempted alkylation of tetronic acids 5 using HC1 in an alcohol or alkyl halides on tetronic acids sodium salts are unsuccessful; moreover, the structure of our compounds 1–3 was questionned by arguing that isomeric 2-alkylated materials     

多种(多元)混合酸的图象计算分析法

以酸碱电位滴定然后进行曲线拟合分析多种(多元)混合酸的方法,可以在不分离的情况下一次滴定分析出多种及多元混合酸的含量和电离常数。Ingman、Johansson、汪葆俊等人已经在这方面做了大量的工作。本文提出了图象计算分析法(即从图形上确定各种酸的pκ_A及个数m,并以线性回归法计算出各个酸的浓度)。这种方法的分析与计算简单、直观、可靠,能有效地应用于实际样品分析。     

N-二异丙氧磷酰化氨基酸的合成

以亚磷酸二异丙酯为磷酰化试剂、次氯酸钠为氯代试剂首次对20种常见的α-氨基酸进行了磷酰化.通过添加适量四丁基溴化铵为相转移催化剂,使用过量的亚磷酸二异丙酯以补偿其在强碱环境中的水解,从而提高了反应产率.所得产物经核磁共振谱、红外光谱和质谱鉴定结构并分析总结了该类化合物的谱图特征规律.     

Dimethylsilicon(IV) Derivatives of Amino Acids

Reactions of dichlorodimethylsilane with the sodium salt of amino acids in 1:2 molar ratio led to the formation of a new series of dimethylsilicon(IV) complexes of general formula, Me 2 SiL 2 [L = anion of amino acids, viz. glycine (HGly), L-methionine (L-MethH), DL- f -alanine (DL- f -AlaH) L-leucine (L-LeuH), L-valine (L-ValH) and D-phenylalanine (D-PheH)]. The complexes have been characterized by elemental analyses, molar conductance, and electronic spectra, and the bonding in these complexes is discussed in terms of their infrared, 1 H and 13 C NMR spectra. A distorted octahedral structure with trans methyl groups has been tentatively suggested for the complexes. The complexes, found soluble in DMSO, have been tested in vitro against various bacteria, viz. Escherichia coli , Pseudomonas putida-2252 , Aeromonas formicans , Staphylococcus aureus-740 , and fungi, viz. Aspergillus niger ORS-4, Aureobasidium pullulans-1991 , Verticillium dahliae-2063 , and Penicillium notatum-1348 .     

Green Synthesis of Poly(aminomethylenephosphonic) Acids

The reaction of polyamines with phosphorous acid and formaldehyde in water under focused microwave irradiation provides a facile and rapid synthesis of poly(aminomethylenephosphonic) acids.     

Synthesis of N-(Homocyclylcarbamoyl)-Maleamic Acids and -Maleimides

A series of N-homocyclylcarbamoyl derivatives of maleamic acid and maleimide was prepared for hypocholesteremic and sulfhydryl-binding tests. The synthetic reactions involved in the controlled aminolysis of maleic anhydride with appropriate mono-substituted ureas and the resulting carbamoylmaleamic acids were then thermally dehydrated to the corresponding carbamoylmaleimides. The monosubstituted ureas required in this synthesis were obtained by the action of amines on isocyanic acid produced in situ from nitrourea on heating in aqueous alcoholic solution.     

Cross-Linking of Poly(α-amino Acids)

Poly(L-leucine) and poly(L-phenylalanine) cross-link with either 2,4-toluene diisocyanate or 1,6-hexane diisocyanate but no such cross-linking resulted for poly(γ-benzyl-L-glutamate). The latter polymer cross-links, however, upon transesterification with diols.     

Synthesis of (3-Indolylsulfanyl)alkanecarboxylic Acids

A method was developed for preparation of (3-indolylsulfanyl)alkanecarboxylic acids from 1H-, 1-methyl(benzyl)-, 2-methylindoles, thiourea, iodine, and halocarboxylic acids.     

Chemistry and Biology of the Zaragozic Acids (Squalestatins)

New natural products seldom arouse much excitement. However, with their unprecedented and heavily oxygenated molecular structure, and potentially lucrative biological activity, the zaragozic acids (squalestatins) provoked a flurry of activity among academic and industrial chemists and biologists in the early 1990s. Since they are powerful inhibitors of squalene synthase, the enzyme catalyzing the first committed step on the biosynthetic pathway to cholesterol, hopes were high that the zaragozic acids would follow the huge commercial success of the mevinic acids by becoming second-generation cholesterol-lowering drugs. The unusual and characteristic 2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid “core” structure of the zaragozic acids stimulated a large number of diverse synthetic studies, ranging from the traditional to the avant garde. In this review we attempt to bring together for the first time the chemistry and biology of this fascinating class of molecules.     

Synthesis,Characterization, and Thermal and Antibacterial Studies of Diorganotin(Iv) Derivatives of Amino Acids

Abstract

Six diorganotin(IV) derivatives of α-aminoacids with general formulae [(CH₃)₂ SnAACl]₂ and [(CH₃CH₂CH₂CH₂)₂SnAACl]₂, where AA = L-alaninate, L-phenylalaninate, and L-isoleucinate, have been synthesized by reacting dimethyltin(IV) dichloride (M) and dibutyltin(IV) dichloride (B) with L-alanine (A) or L-phenylalanine (PA) or L-isoleucine (I) using acetonitrile as the solvent and designated as MA, MPA, MI, BA, BPA, and BI. These complexes have been characterized by elemental analysis, infrared (IR), ¹H NMR, ¹³C NMR, and ¹¹⁹Sn NMR spectroscopy. Thermal studies of all of the synthesized complexes were also carried out using thermogravimetric (TG) and differential scanning calorimetry (DSC) techniques. The thermal decomposition mechanisms were similar for MA, BA, MI, and BI and occurred in one step, while in compounds MPA and BPA, it occurred in two consecutive steps. The TG curves of MPA and BPA suggest the loss of the ligand (AA) in the first step, with probable formation of a tin oxide R₂SnO as an intermediate, and in the second step, free tin is obtained, similar to MA, BA, MI, and BI, in accordance with the stoichiometry of the related derivatives. The diorganotin(IV) complexes have also been screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. The minimum inhibitory concentration values of these complexes show enhanced activity.     

Synthesis, Characterization and Inhibition Effects of Vanadium Substituted Dawson-type Heteropoly Acids(Mo, P)

Four new vanadium substituted Dawson-type heteropoly acids H7[P2Mo17VO62]·39H2O(1), H8[P2Mo16V2O62]·41H2O(2), H9[P2Mo15V3O62]·51H2O(3) and H8[P2Mo14V4O62H2]·45H2O(4) were prepared respec-tively. Their structures were determined by IR and ICP. The inhibition effects of vanadium substituted Dawson-type heteropoly acids(Mo, P) on free radical polymerization of methyl methacrylate(MMA) were investigated by dilatometry. The results show that the rate of the polymerization of MMA decreases and the inhibition effe...     

Study of the Ternary Complex Formation Between Vanadium(III)-Picolinic Acid and the Amino Acids: Cysteine,Histidine, Aspartic and Glutamic Acids

The complex species formed between vanadium(III)-picolinic acid (HPic) and the amino acids: cysteine (H₂Cys), histidine (HHis), aspartic acid (H₂Asp) and glutamic acid (H₂Glu) were studied in aqueous solution by means of electromotive forces measurements emf(H) at 25 °C and 3.0 mol⋅dm⁻³ KCl as ionic medium. Data analysis using the least-squares program LETAGROP indicates the formation of ternary complexes, whose stoichiometric coefficients and stability constant were determined. In the vanadium(III)-picolinic acid-cysteine system the model obtained was: [V(Pic)(H₂Cys)]²⁺, [V(Pic)(HCys)]⁺, V(Pic)(Cys) and [V₂O(Pic)(Cys)]⁺. The vanadium(III)-picolinic acid-histidine system contained the following complexes: [V(Pic)(HHis)]²⁺, [V(Pic)(His)]⁺, V(Pic)(His)(OH) and [V(Pic)₂(HHis)]⁺. In the vanadium(III)-picolinic acid-aspartic acid system the model obtained was: V(Pic)(Asp), [V(Pic)(Asp)(OH)]⁻ and [V₂O(Pic)(Asp)]⁺ and finally, in the vanadium(III)-picolinic acid-glutamic acid system the complexes: V₂O(Pic)₂(HGlu)₂, V(Pic)(HGlu)₂ and V(Pic)₂(HGlu) were observed.