Anisotropic derivatives of (-)-L-lactic acid and their nanocomposites

The paper describes the synthesis and physical-chemical properties of anisotropic derivatives of (-)-L-lactic acid and their nanocomposites. Anisotropic optically active aryl (S)-2-(ω-halogenalkoxy)lactates and (R)-2-aryloxypropionic acids have been synthesised by the modification of corresponding 3,6-disubstituted cyclohex-2-enones, (-) ethyl L-lactate and ethyl esters of (S)-2-(4-bromobutoxy)- and (S)-2-(6-bromohexyloxy)propionic acids. The optically active (R)-2-aryloxypropionic acids were used for the preparation of mesomorphic nanocomposite materials and their properties were studied. Anisotropic materials based on the derivatives of lactic acid are capable to interact with inorganic nanoparticles providing a tool for the creation of new nanocomposite materials.     

含氟β-氨基酸及其衍生物的合成进展

含氟β-氨基酸及其衍生物具有特殊的生理活性, 其合成方法的研究近年来受到广泛关注. 以直接氟化法和间接氟化法分类, 概述了含氟β-氨基酸及其衍生物的合成方法及最新研究进展, 对一些已知化合物的生理活性及药用价值作了初步归纳.     

Determination of amino acids in human blood serum by reversed-phase high-performance liquid chromatography in the isocratic elution mode

A procedure is developed for the determination of 15 amino acids in human blood serum usingortho-phthalic aldehyde in combination with 2-mercaptoethanol or sodium sulfite as the reagent for the precolumn synthesis of derivatives with their subsequent separation by reversed-phase high-performance liquid chromatography in the isocratic elution mode using electrochemical detection. Conditions of the quantitative conversion of amino acids to corresponding derivatives were determined;ortho-phthalic—mercaptoethanol andortho-phthalic/sulfite derivatives of amino acids are stable during the whole cycle of analysis. The total time of separation is 80 min. The detection limits are 0.5-5 pmol (at the signal-to-noise ratio equal to 2). The procedure is used for the determination of glutamic acid, asparagine, serine, glutamine, histidine, taurine, alanine, arginine, methionine, isoleucine, ornithine, leucine, phenylalanine, lysine, and tryptophane in blood serum of healthy donors and of sick with alcoholism before and after treatment     

Synthesis and Acidity of 5-Phenyltetrazol-2-ylalkanoic Acids and the Corresponding 5-(5-Phenyltetrazol-2-ylalkyl)tetrazoles

We have obtained 5-phenyltetrazol-2-ylalkanoic acids and their derivatives containing terminal nitrile, amide, and tetrazol-5-yl groups. Tetrazolylalkanoic acids with two (pK _a 4.93) and three (pK _a 5.45) bridging methylene groups are weaker acids than the corresponding ditetrazoles pK _a 4.68 and 5.29 respectively). However, the acidity of 5-phenyltetrazol-2-ylacetic acid (pK _a 3.12), is higher than acidity of the corresponding ditetrazole (pK _a 3.27).     

Derivatives of 1-aryl-5-methoxyindoles

By fusion with potassium hydroxide, derivatives of 1-aryl-3-ethoxycarbonyl-5-methoxy-2-methylindole are converted into the corresponding indole-3-carboxylic acids. When the indole-3-carboxylic acids are heated to their melting points, they are readily converted into derivatives of 1-arylindoles with unsubstituted -positions. A similar cycle of conversions has been carried out for 3-ethoxycarbonyl-5-methoxy-2-methyl-1-phenylbenzoindole. The reactions of derivatives of 1-aryl-5-methoxy-2-methylindoles with formaldehyde and dimethylamine hydrochloride gives Mannich bases.     

Carbon-13 NMR spectra and the method for their calculation for long-chain polybranched carboxylic acids and their derivatives

Carbon-13 NMR spectra of 56 long-chain polybranched carboxylic acids their esters, including chloroand acetoxy-substituted derivatives, have been studied. An empirical linear two-parameter equation, relating carbon chemical shifts in α-branched carboxylic acids and their derivatives to the chemical shifts of the corresponding carbon atoms in analogous hydrocarbons, and to the degree of branching at the α-carbon atom, is suggested for the assignment of the signals, where δ_X is the shift in the acid (ester), δ_H the shift in its hydrocarbon counterpart and n the degree of branching. The regression coefficients, A, B and C, are given for X=COOH, COOMe and COOEt. It is shown that with polysubstituted derivatives, the equation may be applied sequentially. The secondary coefficients for the α-substituent then depend on the nature of the substituent X entering the primary equation. The equation may, if necessary, be applied in combination with the additive and structural increments of halogen atoms.     

Determination of 30 Free Fatty Acids in Two Famous Tibetan Medicines by HPLC with Fluorescence Detection and Mass Spectrometric Identification

A simple and sensitive high-performance liquid chromatographic (HPLC) method with fluorescence detection and mass spectrometric identification has been developed for analysis of 30 long-chain and short-chain free fatty acids (FFAs). The fatty acids were derivatized to their esters with 1-[2-(p-toluenesulfonate)ethyl]-2-phenylimidazole-[4,5-f]-9,10-phenanthrene (TSPP) in N,N-dimethylformamide (DMF) at 90 °C with anhydrous K₂CO₃ as catalyst. A mixture of C₁–C₃₀ fatty acids was completely separated within 60 min by gradient elution on a reversed-phase C₈ column. Qualitative identification of the acids was performed by atmospheric-pressure chemical ionization mass spectrometry (APCI–MS) in positive-ion mode. The fluorescence excitation and emission wavelengths were 260 and 380 nm, respectively. Quantitative determination of the 30 acids in two Tibetan medicines Gentiana straminea and G. dahurica was performed. The results indicated that the medicines contained many FFAs. Linear correlation coefficients for the FFA derivatives were >0.9991. Relative standard deviations (RSDs, n = 6) for the fatty acid derivatives were <3%. Detection limits (at a signal-to-noise ratio of 3:1) were 3.1–38 fmol. When the fatty acid derivatives were determined in the two real samples results were satisfactory and the sensitivity and reproducibility of the method were good.     

A facile synthesis of 3-aryl-4-pyrazoleacetic acids and of their 4,5-dihydro derivatives

N-1-Unsubstituted-3-aryl-4-pyrazoleacetic acids and their 4,5-dihydro derivatives can conveniently be prepared by cyclization of 3-benzoyl-3-butenoic acids with hydrazine hydrate in acetic acid and subsequent treatment with bromine in acetic acid or, respectively, with diluted mineral acids.     

Synthesis of new types of aminomethylenediphosphorus-containing acids and their derivatives

Convenient methods for synthesis of various aminomethylenediphosphorus-containing acids and their derivatives starting from available trimethylsilyl esters of hypophosphorous and phosphorous acids, ethoxymethyleneimine hydrochlorides, and N-substituted formamides have been proposed. Selected properties of the obtained compounds have been examined.

     

Optical rotatory dispersion and circular dichroism. LXXV. Circular dichroism of some aryl-amino acids

CD. curves have been recorded for α-aryl-α-amino acids, esters and amides related to α-phenylglycine, α-phenyl-alanine and their N-dimethyl derivatives, and for the corresponding α-cyclohexyl-α-amino acids and esters. Compounds with the (S)-configuration at the single asymmetric carbon atom give strong positive Cotton effects near 220 nm. The conformations of the acids are discussed and compared with those of other α-amino acids.     

Studies in the heterocyclic series XVII. A new type of triazaphenothiazine heterocycle

The synthesis of derivatives of 1,4,6-benzo[b]triazaphenothiazine, a novel aza-analog of phenothiazine, is described. The parent compound was obtained by base-catalysed condensation of 3-amino-2-mercaptopyridine with 2,3-dichloroquinoxaline in aqueous DMF. Several derivatives were also prepared by using the appropriately substituted aminomercaptopyridines and dichloro-quinoxalines. Nitration with mixed nitric and sulfuric acids gave the corresponding 13-nitro-1,4,6-benzo[b]triazaphenothiazine derivatives. The structures were elucidated by chemical evidence and by a study of their infrared, ultraviolet, pmr and mass spectra.     

Synthesis of isocoumarin, 1-isoquinolone and 4(1H)-quinolone derivatives via seleno-intermediates

The reaction of 2-styrylbenzoic acids 2 with N-phenylselenosuccinimide (N-PSS) affords 3-phenyl-iso-coumarin derivatives 3 and 3,4-dihydro-3-phenyl-4-(phenylseleno)isocoumarins 4 via selenolactonization. The reaction of 2-styrylbenzamides 5 and 1-(2-aminophenyl)-3-phenyl-2-peropen-1-one derivatives 11 with N-PSS also resulted in the formation of 1-isoquinolone 6 and 4(1H)-quinolone derivatives 12 , respectively.     

Synthesis and transformations of derivatives of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acid

On the basis of methyl esters of 2-aryl-5-hydrazino-1,3-oxazole-4-carboxylic acids the earlier unknown methyl esters of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acids as well as their functional derivatives were synthesized. The latter were used for further transformations, in particular, for introducing the residues of highly basic aliphatic amines into the 5 position of oxazole, and the oxazol-2-yl moiety into the 4 position of the oxazole ring.     

Design and Synthesis of Some New α‐Phenyl Cinnamoyl Derivatives for Selective Protection of Purine Nucleosides

Three new α‐phenylcinnamic acid derivatives [4‐methoxy‐α‐phenylcinnamic acid, α‐(4‐methoxyphenyl)‐cinnamic acid, and 4,4′‐bismethoxy‐α‐phenylcinnamic acid] were synthesized, characterized, and selectively used for protecting the exocyclic amino function of purine nucleosides (2′‐deoxyadenosine and 2′‐deoxyguanosine) via active ester generation. The acids were first activated using p‐nitrophenol, and these activated esters were used subsequently for the selective protection of amino groups. The N‐protected derivatives of 2′‐deoxyguanosine and 2′‐deoxyadenosine have been found to be sufficiently stable toward acids, thus minimizing depurination under oligodeoxyribonucleotide synthesis protocol. The ease of syntheses of N‐protected purine nucleosides, their stability under an acidic environment, and mild deprotection conditions are the key advantages of the new protecting groups.     

3-Fluoroalkyl (CF3, CHF2, CH2F) Cyclobutane-Derived Building Blocks for Medicinal Chemistry: Synthesis and Physicochemical Properties

Synthesis and physicochemical characterization of all possible cis- and trans-1,3-disubstituted cyclobutane-derived amines and carboxylic acids bearing mono-, di- and trifluoromethyl groups at the C-3 position is disclosed. Tetramethylammonium fluoride (TMAF)- or morpholinosulfur trifluoride (Morph-DAST)-mediated nucleophilic fluorination of appropriate cis- and trans-diastereomeric substrates was used as the key step for the preparation of CH₂F- and CHF₂-substituted derivatives. To obtain the corresponding cis- and trans-isomeric CF₃-substituted derivatives, resolution of known 3-(trifluoromethyl)cyclobutanecarboxylic acid (obtained as a mixture of diastereomers) was applied. The proposed procedures were suitable for the preparation of corresponding fluoroalkyl-substituted cyclobutane-derived amines and carboxylic acids on up to 50 g scale. All 12 building blocks obtained were characterized by measuring dissociation constants (pK_a) and lipophilicities (LogP, for model derivatives) to evaluate the effect of the fluoroalkyl substituents on their physicochemical properties relevant to further drug discovery applications.     

NMR spectroscopy in distinguishing between 3-piperidyl- and 2-pyrrolidylmethyl alcohols,amines, esters,and amides

Nmr analysis was found to be superior to an older ir technique for assigning structures in a study involving ring contraction-expansion of 3-hydroxypiperidine ? 2-hydroxymethylpyrrolidine systems and their ester derivatives. Nmr was not useful in studies of 3-aminopiperidines and 2-aminomethylpyrrolidines, but it could be applied to certain of their N-acyl derivatives. The nmr method was used to determine that esterification reactions of 1-methyl-3-(p-toluenesulfonyl)-piperidine and the sodium or potassium salts of some highly substituted carboxylic acids gave the ring-contracted pyrrolidine esters. In contrast, 1-methyl-3-aminopiperidine formed an amide with benzilic acid in which the piperidine ring remained unchanged. Aminolysis of methyl benzilate with 1-methyl-3-aminopiperidine resulted in a novel decarbonylation of the ester and isolation of benzophenone and l-methyl-3-formylamidopiperidine.     

Linear free energy ortho-correlations in the thiophene series. Part IX . Kinetics of esterification with diazodiphenylmethane of some 3-, 4-, and 5-substituted thiophene-2-carboxylic acids in methanol

The rate constants for the esterification of some 3-, 4-, and 5-substituted thiophene-2-carboxylic acids with diazodiphenylmethane in methanol at 25° have been measured. The reactivity of some para- and ortho-substituted benzoic acids has also been determined. Logarithmic kinetic constants for ortho-, meta-, and para-like substituted thiophene-2-carboxylic acids furnish an excellent linear free energy relationship when plotted versus Δpk_a (β 0.89, r 0.989, C.L. > 99.9%, n 18, i 0.04), thus confirming the peculiar behaviour of five-membered ring derivatives. The correlation with σ^H values offers an additional proof of the hyper-ortho character of the 2,3-relation in thiophene derivatives. para- and ortho-Substituted benzoic acids show the usual behaviour of six-membered ring derivatives.     

Direct Phosphorylation of N-Protected Imidazoles and Benzoimidazoles-A Route to 1H-Imidazol(benzoimidazol)-2-yl Phosphonic and Phosphinic Acids and Their Derivatives

Synthetic approaches to 1H-imidazol-2-yl and 1H-benzoimidazol-2-yl phosphinic and phosphonic acids and their derivatives are reported, based on phosphorylation of N-protected heterocylcles by PhPOCl₂ or MePOCl₂. Reaction of N-alkylbenzoimidazoles with POCl₃ did not lead to C-phosphorylated products in a reasonable yield, [2,2′]-bis-benzoimidazolyles being formed instead.     

Structure-Property Relationship: VIII. Estimation of log P for Amides of Carboxylic Acids and Their N-Acetyl Derivatives

A structure-property relationship is proposed, that allows a fairly accurate estimation of log P for amides of carboxylic acids and their N-acetyl derivatives.     

Asymmetric and Geometry‐Selective α‐Alkenylation of α‐Amino Acids

Both E‐ and Z‐N′‐alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α‐amino acids. Generation of their enolate derivatives in the presence of K⁺ and [18]crown‐6 induces intramolecular migration of the alkenyl group from N′ to Cα with retention of double bond geometry. DFT calculations indicate a partially concerted substitution mechanism. Hydrolysis of the enantiopure products under acid conditions reveals quaternary α‐alkenyl amino acids with stereodivergent control of both absolute configuration and double bond geometry.