Enantiomeric Recognition of d- and l-Amino Acid Methyl Ester Hydrochlorides by New Chiral Bis-pyridino-18-crown-6 Substituted with Urea, and Diphenyl Groups

The article reports the synthesis and chiral recognition properties of a new chiral bis-pyridino-18-crown-6 (7), having urea, diphenyl, and allyloxy groups. The chiral bis-pyridino-18-crown-6 was prepared by a thirteen-steps procedure from the commercially available (S)-(+)-mandelic acid and chelidamic acid. The association constants (K _a) (1.33 × 10³–3.20 × 10³) for enantiomeric recognition of d- and l-amino acid methyl ester hydrochlorides using the chiral bis-pyridino-18-crown-6 have been examined by ¹H-NMR titration method in CDCl₃ at 25 °C. The chiral bis-pyridino-18-crown-6 showed higher association constants for the d-series amino acid methyl ester (d-AlaOMe, d-LeuOMe, d-MetOMe) hydrochlorides as compared to the corresponding l-series (l-AlaOMe, l-LeuOMe, l-MetOMe) hydrochlorides.     

Determination of Binding Constants of Polyethylene Glycol Vancomycin Derivatives to Peptide Ligands Using Affinity Capillary Electrophoresis

Vancomycin (Van) from Streptomyces orientalis has been derivatized with polyethylene glycol [PEG; PEG-550 (1), 750 (2), 1,100 (3), 2,000 (4), 5,000 (5), and 8,000 (6) g mol⁻¹] at the N-terminus of the glycopeptide backbone and their binding to d-Ala-d-Ala terminus peptides assessed using affinity capillary electrophoresis (ACE). Utilizing ACE, a plug of Van-PEG and non-interacting standards are injected and electrophoresed. Analysis of the change in the relative migration time ratio of the Van-PEG species, relative to the non-interacting standards, as a function of the concentration of peptide, yields a value for the binding constant (K _b). Values of K _b for N-acetyl-d-Ala-d-Ala, 7 to the Van-PEG derivatives are weaker than those for N _α,N _ε-diacetyl-Lys-d-Ala-d-Ala, 8 (for example, values of K _b for 7-1 and 8-1 are 1.8 and 47.7 × 10³ M⁻¹, respectively). These results demonstrate that derivatization of Van with PEG has little effect on the affinity of d-Ala-d-Ala peptide ligands to it. The findings further prove the versatility of ACE and its ability to estimate binding parameters of ligands to antibiotics.     

Synthesis and amino acid extraction abilities of chiral calix[4]arene triamides containing amino alcohol units

Herein the synthesis and extraction abilities of new d-/l-phenylalaninol substituted p-tert-butylcalix[4]arene triamide derivatives (3 and 4) towards amino acids are reported. These compounds (3 and 4) have been easily synthesized via aminolysis of p-tert-butylcalix[4]arene trimethylester (2) with d-/l-phenylalaninol in methanol-toluen solvent system at one step. The extraction properties of the prepared chiral calix[4]arene triamide derivatives (3 and 4) towards some selected amino acid methylesters are studied by liquid–liquid extraction. Results show that these chiral calix[4]arene triamide derivatives (3 and 4) exhibited a good affinity towards all amino acid species without any remarkably discrimination.     

Synthesis and complex-forming properties of crown ethers incorporating glucuronic acid moieties

Crown ethers1 and4 of the 18-crown-6 type containing two glucose units have been oxidised by KMnO₄ into mono- and dicarboxylic acid derivatives (5 and11), and derivatives with different lipophilicities of the above crown ethers, namely the acetyl, benzyl and butyl derivatives (8–10, 13, 14) and methyl esters (6 and12) have been synthesizedThe association constants (K _a) with Li, Na, K and NH₄ cations measured in CHCl₃ indicate that complexing ability increases on introduction of carboxy groups, and selectivity changes in favour of the Na cation. These compounds were able to transport alkyl-ammonium salts through a CHCl₃ liquid membrane, displaying, however, no chiral recognition ability.     

某些官能化手性氮杂环丙烷衍生物的合成及其结构

手性元5-(R)-(1R,2S,5R)-孟氧基-3-溴-2(5H)-呋喃酮(3)与氮亲核试剂伯胺(4), 通过串联的不对称Michael加成/分子内亲核取代反应得到了具有两个新的手性中心的1R,5S-6-烷基-6-氮杂-2R-孟氧基-3-氧杂-4-氧代二环[3,1,0]己烷(5a～5d), 产率41%～51%, e.e.≥98%. 后者经LiAlH₄还原得到N-烷基-2,3-双(羟甲基)氮杂环丙烷(6a～6d), 产率66%～91%. 化合物5和6通过元素分析, IR, ¹H NMR, ¹³C NMR, MS以及X射线晶体分析, 测定了它们的化学结构及立体化学构型. 本文为N-烷基氮杂环丙烷类化合物的合成提供了一种有效途径.     

Synthesis,ABTS-Radical Scavenging Activity,and Antiproliferative and Molecular Docking Studies of Novel Pyrrolo[1,2-a]quinoline Derivatives

A new 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-radical scavenging and antiproliferative agents of pyrrolo[1,2-a]quinoline derivatives have been synthesized. An efficient method for the synthesis of 14 novel diversified pyrrolo[1,2-a]quinoline derivatives has been described using 4-(1,3-dioxolan-2-yl)quinoline and different phenacyl bromides in acetone and followed by reacting with different acetylenes in dimethylformamide/K₂CO₃. The structure of the newly synthesized compounds was determined by infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The in vitro antioxidant activity revealed that among all the tested compounds 5n exhibited maximum scavenging activity with ABTS. Compound 5b has showed good antiproliferative activity as an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase.     

Synthesis of chiral SalenZn(II) and its coordination with imidazole derivatives and amino acid ester derivatives

A chiral complex, SalenZn(II) (S), was synthesized and characterized. Its coordination with imidazole derivatives and amino acid ester derivatives was studied by UV-vis spectrophotometric titrations and CD spectroscopy. The binding constants decreased in the order K (Im)>K (2-MeIm)>K (2-Et-4-MeIm)>K (N-MeIm) for imidazole derivatives, and K (AlaOMe)>K (PheOMe)>K (ValOMe) for amino acid ester derivatives with the same configuration and K _D >K _L for amino acid esters with different configuration. CD spectra can quantify the strength of SalenZn(II)-ligand interactions, giving results consistent with the magnitudes of the binding constants. Moreover the minimum energy conformations of the adducts were obtained by simulated annealing, and quantum chemical calculations were performed based on those conformations to explain experimental results at the molecular level.     

含吡啶的抗肿瘤转移NAMI-A衍生物的制备和水解机理动力学

目的研究配体结构对NAMI-A衍生物水解机理、电化学性质的影响。方法制备了trans-[RuCl4(DMSO)(3-MePy)][(3-MePy)H](3-MePy=3-甲基吡啶,化合物1)和trans-[RuCl4(DMSO)(4-MePy)][(4-MePy)H](4-MePy=4-甲基吡啶,化合物2)。用UV、NMR、CV法研究化合物1、化合物2的水解机理-动力学、溶液稳定性及电化学性质。结果化合物1和化合物2与NAMI-A相似,在pH7.40的缓冲液中发生脱氯水解反应(Ⅰ氯水解及Ⅱ氯水解)(分步反应);在pH 5.00缓冲液中DMSO(二甲亚砜)及少量吡啶水解。测定各水解反应表观速率常数及半衰期、溶液稳定性及氧化还原电位。结论化合物1、化合物2的Ⅰ氯、Ⅱ氯及DMSO水解反应机理与NAMI-A相似,而且各水解速率与NAMI-A相差不大,即用甲基吡啶取代咪唑环,对NAMI-A衍生物的Ⅰ氯、Ⅱ氯及DMSO水解反应速率影响较小。化合物在酸性溶液中的稳定性明显高于中性溶液。     

Estimation of binding constants between ristocetin and teicoplanin and peptides using on-column ligand derivatization coupled to affinity capillary electrophoresis

This work utilizes on-column ligand synthesis and affinity capillary electrophoresis (ACE) to determine binding constants (K_b) of 9-flourenylmethyloxy carbonyl (Fmoc)-amino acid derivatives to the glycopeptide antibiotics ristocetin (Rist) and teicoplanin (Teic). In this technique, two separate plugs of sample are injected on to the capillary column and electrophoresed. The initial sample plug contains a d-Ala-d-Ala terminus peptide and either one or two non-interacting standard(s). The second plug contains a Fmoc-amino acid-N-hydroxysuccinimide (NHS) ester. The electrophoresis is then carried out with an increasing concentration of Rist or Teic in the running buffer. Upon electrophoresis the initial d-Ala-d-Ala peptide reacts with the Fmoc-amino acid yielding a new Fmoc-amino acid-d-Ala-d-Ala peptide derivative. Continued electrophoresis results in the binding of Rist or Teic to the Fmoc-amino acid-d-Ala-d-Ala peptide derivatives. Analysis of the change in the relative migration time ratio (RMTR) or electrophoretic mobility () of the Fmoc-amino acid-d-Ala-d-Ala peptide derivatives relative to the non-interacting standards, as a function of the concentration of Rist and Teic, yields a value for K_b. These findings demonstrate the advantage of coupling on-column ligand synthesis to ACE for estimating binding parameters between antibiotics and ligands.Abbreviations Rist Ristocetin - Teic Teicoplanin - ACE Affinity capillary electrophoresis - RMTR Relative migration time ratio     

Mass Spectrometric Determination of Association Constants of Bovine Serum Albumin (BSA) with para-Sulphonato-Calix[n]arene Derivatives

Electrospray Ionization Mass Spectrometry (ESI/MS) has been used to determine the association constants (K_As) and binding stoichiometries for parent para-Sulphonato-calix[n]arenes and their derivatives with bovine serum albumin (BSA). K_A values were determined by titration experiments using a constant concentration of protein. K_A measurements were carried out in a methanol–formic acid solution. 5,11,17,23–tetra-Sulphonato-calix[4]arene (1a) and 25-mono-(2-aminoethoxy)-5,11,17,23-tetra-Sulphonato-calix[4]arene (1d) interact strongly with BSA showing 3 non-equivalent binding sites with K_A1 = 7.69 × 10⁵ M⁻¹, K_A2 = 3.85 × 10⁵ M⁻¹, K_A3 = 0.33 × 10⁵ M⁻¹ and K_A1 = 1.69 × 10⁵ M⁻¹, K_A2 = 2.94 × 10⁵ M⁻¹, K_A3 = 0.60 × 10⁵ M⁻¹, respectively. The strength of the interactions between the calixarene and BSA is inversely proportional to the size of macrocyclic ring: n = 4 > n=6>>n=8.     

Computer estimation of dissociation constants. Part IV. Precision and accuracy of potentiometric determinations

The protonation constants logK _Hj of the acidH _J are determined by regression analysis of potentiometric titration data whencommon parameters (logK _Hj,j = 1,...,J) andgroup parameters (E ⁰,L ₀,H _T ) are refined. Two kinds of systematic error have been investigated: the error from an uncertainty of group parameters and the error from a computational strategy of the minimization algorithm used. An analysis of variance of logK _Hj matrix was made for 6 reproduced titrations and 7 computational strategies of 6 various regression programs. It was concluded that the influence of the program used is negligible. From two ways of calibration of the glass electrode cell,the internal calibration (performed during titration) was slightly more accurate thanthe external calibration (done separately). Of programs tested, the ESAB and ACBA are most powerful because they permit refinement of group parameters and internal calibration. D-tartaric acid was chosen as model substance.Previous Part III.: Iraqi J. Sci.1981,22, 67.     

Synthesis of diblock copolymers with cellulose derivatives. 3. Cellulose derivatives carrying a single pyrene group at the reducing-end and fluorescent studies of their self-assembly systems in aqueous NaOH solutions

Novel cellobiose and cellulose (DP _n =ca. 30) derivatives, N-(1-pyrenebutyloyl)-4-O-(β-d-glucopyranosyl)-β-d-glucopyranosylamine (6), N-(15-(1-pyrenebutyloylamino)-pentadecanoyl)-4-O-(β-d-glucopyranosyl)-β-d-glucopyranosylamine (7), N-(1-pyrenebutyloyl)-β-cellulosylamine (13), N-(15-(1-pyrenebutyloylamino)-pentadecanoyl)-β-cellulosylamine (14) carrying a pyrene group as a single fluorescent probe at the reducing end, were prepared in order to investigate their self-assembly systems in solutions. The relative intensity of the excimer emission at ca. 480 nm due to dimerized pyrenes (intensity I _E) to the monomer emission at ca. 380 nm due to isolated pyrene (intensity I _M), i.e., I _E/I _M, was monitored in various solutions. In water/dimethyl sulfoxide (DMSO) mixed solvent (0–98%, v/v), the ratio I _E/I _M remained low (0.04) for compound 6 over the range of water concentrations, indicating that pyrenes at C-1 position of compound 6 were diffused. On the other hand, the ratio I _E/I _M increased (0.04–4.96) for compound 7 with the increase in water concentration, indicating that pyrenes at C-1 position were associated. In aqueous NaOH solutions (4.4–17.5%, w/w), compound 14 showed a large increase in the ratio I _E/I _M (0.84–8.14) with the increase in NaOH concentration, compared to compound 13 (0.06–0.41). It was found that the association of hydrophobic groups at the reducing-end of cellulose could be controlled by the hydrophilic–hydrophobic balance of compounds and the solvent polarity.     

Efficient Synthesis of Novel 3-[5-(1H-Benzimidazol-2-Ylmethanesulfonyl)-4-Phenyl-4H-(1,2,4)Triazol-3-Yl]-1H-(1,8)Naphthyridin-4-One Derivatives

Abstract

of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1 h resulted in 3-(5-mercapto- 4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from following sequence of reactions, i.e., 4 → 8 → 7. In another sequence of reactions, condensation of 7 with chloroacetic acid in dimethylformamide (DMF) and K₂CO₃ as a mild base at 120 °C for 2 h resulted in 2-((5-(1,4-dihydro-4-oxo-1,8-naphthyridin-3-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)sulfanyl)acetic acid (10). The latter, on reaction with substituted o-phenylenediamine (11) in 6N HCl for 4 h yielded 3-(5-((1H-benzo[d]imidazol-2-yl)methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (12). Alternatively, 12 could also be prepared by reacting 7 with 13 in DMF and K₂CO₃ as a mild base at 120 °C for 2 h, followed by oxidation with H₂O₂ resulting in the corresponding sulfonyl derivatives 14.     

Synthesis and Host Properties of (1,3)- p-tert-Butylcalix[5]crown-6 Derivatives Incorporating the 1,1'-Binaphthalene-2,2'-dioxy Subunit

Alkylation of p-tert-butylcalix[5]arene (1) with 2,2'-bis(5-tosyloxy-3-oxa-1-pentyloxy)-1,1'-binaphthalene ((±)-2) in the presence of CsF affords selectively racemic 1,3-bridged calix[5] [5]crown-6-triol 3, along with very small amounts of the (1,2)-bridged regioisomer 4. Compound 3 has been converted into tri-methoxy and tri--picolyloxy derivatives 5 and 6, respectively, by exhaustive alkylation with the appropriate electrophile and base. The direct separation of the enantiomers of racemates 3 and 6 was achieved by HPLC, using a chiral stationary phase (Chiralpak AD). Hosts 5 and 6 are able to selectively form 1 : 1 endo-cavity complexes with the linear RNH₃ ⁺ ions.     

Synthesis of Andrographolide Cyclophosphate Derivatives and Their Antitumor Activities

A series of cyclophosphate andrographolide derivatives were synthesized from andrographolide, the cytotoxic constituent of the plant Andrographis paniculata. The derivative (P_R, P′_S)‐5 and (P_S, P′_S)‐6 were synthesized and the proposed mechanism for their formation was discussed. The structures of all compounds were elucidated by IR, NMR, MS (ESI), and HR‐MS. The stereochemistry of 6 was confirmed by X‐ray analysis. All the derivatives were tested for antitumor activity in vitro, and some of them showed good results.     

Potentiometric and Voltammetric Study of 6‐Benzylaminopurine and Its Derivatives

The protonation‐deprotonation equilibrium of 6‐benzylaminopurine (6‐BAP) and its derivatives was studied by potentiometry and voltammetry. The effect of Cl‐ or OCH₃‐group in position 2′, 3′ and 4′ of the benzene ring of 6‐BAP on both pK_a values was investigated. To determine the enthalpy and entropy, the temperature dependence of pK_a was employed. It was found that with increasing temperature the pK_a decreased. In comparison with 6‐BAP the chloro‐ or methoxy‐ group resulted in pK_a increase. The first pK_a values were also determined by linear sweep (LSV) and elimination voltammetry with linear scan (EVLS). New approaches were shown not only for the determination of pK_a from voltammetric titration curves but also for the evaluation of the reduction processes of benzylaminopurines.     

Synthesis and Antiviral Activities of Chiral Thiourea Derivatives

An environmentally benign method has been developed for the synthesis of novel chiral thiourea derivatives in high yields in ionic liquid [Bmim]PF6. The ionic solvent can be recovered and reused without any loss of its activity. The target compounds were characterized by elemental analysis, IR, 1H NMR and 13C NMR spectral data. According to the preliminary bioassay, some of the chiral thiourea analogues exhibited moderate in vivo antiviral activities against TMV at a concentration of 500 mg/L. Title chiral compound 3i was found to possess good in vivo protection, inactivation and curative activities of 57.0%, 96.4% and 55.0%, respectively against TMV with an inhibitory concentration at 500 mg/L. The title chiral compound 3i revealed better inactivation effect on TMV (EC50＝50.8 µg/mL) than Ningnanmycin (EC50＝60.2 µg/mL).     

Synthesis and Properties of New Thiacalixarene Derivatives with Palladium Ion

Three new thiacalix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl-25,27-di(2-hydroxyethoxy)-26,28-dihydroxythiacalix-{}[4]arene (2), 5,11,17,23-tetra-tert-25, 26,27,28-tetrakis[(methylcarboxyl)methoxy]thiacalix[4]arene (3),5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis(2-hydroxy-1-propanoxy)thiacalix[4]arene (4), were synthesized for the first time. The coordination properties of thiacalix[4]arene(1) and its derivatives (2 and 4) were investigated by detecting the interactions betweenthese compounds and two palladium complexes, cis-[Pd(en)(H₂O)₂]²⁺ and cis-[Pd(dtco-3-OH)(H₂O)₂]²⁺, by means of electrospray ionization mass spectrometry (ESI-MS) technique.     

Preparation of Regioselectively Modified Amylose Derivatives and Their Applications in Chiral HPLC

Four regioselectively modified amylose derivatives with three different substituents at the 2-, 3-, and 6-positions were prepared and their enantioseparations in HPLC were examined. Investigations indicated that the nature as well as the arrangement of the substituents significantly influenced their enantioseparations and each derivative exhibited characteristic chiral recognition. Amylose 2-benzoyl-3-(3,5-dimethylphenylcarbamate or 3,5-dichlorophenylcarbamate)-6-((S)-1-phenylethylcarbamate) exhibited chiral resolving abilities comparable to the commercial available amylose tris(3,5-dimethylphenylcarbamate)-based column, Chiralpak AD and the racemic compounds shown in this study were most effectively resolved on these two derivatives. The influence of mobile phase on chiral resolution was also examined.

     

Enantioselective Addition Reaction of Azlactones with Styrene Derivatives Catalyzed by Strong Chiral Brønsted Acids

An enantioselective intermolecular addition reaction of azlactones, as carbon nucleophiles, with styrene derivatives, as simple olefins, was demonstrated using a newly developed chiral Brønsted acid catalyst, namely, F₁₀BINOL‐derived N‐triflyl phosphoramide. Addition products having vicinal tetrasubstituted carbon centers, one of which is an all‐carbon quaternary stereogenic center, were formed in good yields with moderate to high stereoselectivities. Extremely high acidity of the new chiral Brønsted acid was confirmed by its calculated pK_a value based on DFT studies and is the key to accomplishing not only high catalytic activity but also efficient stereocontrol in the intermolecular addition.