Detailed studies on the reduction of aliphatic 3-, 4-, 6-, and 13-oximino esters: Synthesis of novel isomeric amino esters,oximino alcohols,and amino alcohols

The preparation of novel 3-, 4-, 6-, and 13-amino-tetradecanoic acid methyl esters (2a–d) obtained by the reduction of 3-, 4-, 6-, and 13-oximino-tetradecanoic acid methyl esters (1a–d), was investigated. Oximino esters were reduced to afford the corresponding amino esters using NaBH₄–ZrCl₄ reducing system with good yields (58–82%). However, the reduction of oximino esters with LiAlH₄ and BH₃. Tetrahydrofuran gave the corresponding novel 3-, 4-, 6-, and 13-oximino alcohols (3a–d), and 3-, 4-, 6-, and 13-amino alcohols (4a–d) respectively with good chemical yields.     

Influence of the Addition of Lauric Acid to Films Made from Gelatin,Triacetin and a Blend of Stearic and Palmitic Acids

Summary: The objective of this research was to verify the influence of adding increasing amounts of lauric acid on the functional properties of homogenized films made from gelatin, triacetin and a blend of palmitic and stearic acids. The films were characterised with respect to their visual aspect, water vapour permeability (WVP), water solubility, mechanical properties (tensile strength and percent elongation), oxygen permeability (O₂P), opacity (OP) and melting and glass transitions temperatures. The films produced were malleable and macroscopically homogeneous. The addition of 1% of lauric acid to the film of gelatin, triacetin and blend of palmitic and stearic acids (5.84 ± 0.31 gmm · m⁻² dkPa) caused a slight decrease in WVP. The additions of 2.5% (5.70 ± 0.76 gmm · m⁻² dkPa), 5% (5.38 ± 0.64 gmm · m⁻² dkPa) and 10% (4.50 ± 0.55 gmm · m⁻² dkPa) of lauric acid were sufficient to make a significant difference in the WVP at the higher levels used. As compared to the gelatin and triacetin film, the addition of lauric acid at all the concentrations studied resulted in a slight increase in the film solubility. The addition of hydrophobic substances to gelatin/triacetin films (15.26 ± 0.28 cm³ · µm · m⁻² dkPa) favoured an increase in O₂P permeability, this effect being greater in the films made from gelatin, triacetin, blend of palmitic and stearic acids and 10% lauric acid (24.48 ± 0.07 cm³ · µm · m⁻² dkPa). The increasing addition of lauric acid significantly reduced the tensile strength and increased elongation of the films composed of gelatin, triacetin and blend that being more evident at the concentrations of 5% (67.58 ± 1.23 MPa and 11.45 ± 0.57%) and 10% (63.50 ± 1.56 MPa and 12.90 ± 0.57%). The addition of 1% (OP, 27%) and 10% (OP, 28%) of lauric acid induced no visible effect on the opacity of the films. The thermogrammes showed three transitions for the gelatin/triacetin/stearic-palmitic blend/1% lauric acid films (−57.42 °C, 23.74 °C and 44.11 °C) and two for the gelatin/triacetin/stearic-palmitic acids blend/10% lauric acid films (−56.22 °C and 17.35 °C). As observed by DSC, the addition of fatty acids resulted in the appearance of more than one melting peak for all films in relation to the gelatin and triacetin film.     

Conductimetric Assay of a Bacterial Lipase,Using Triacetin as a Substrate

Abstract

A conductimetric method has been applied to measure lipase activity. When using triacetin as a substrate, a linear relationship between initial rate and enzyme concentration is demonstrated up to 600 U in the cell (4 ml). Kinetic parameters of triacetin hydrolysis have been derived from conductimetric data, in the concentration range of solubility of the substrate. The limiting parameters (temperature, choice of buffer, substrate) are discussed in the last part.     

Radiation-induced polymerization of glass-forming systems. V. Initial polymerization rate in binary glass-forming systems

The radiation-induced polymerization of binary systems consisting of glass-forming monomer and glass-forming solvent in supercooled phase was studied. The initial polymerization rates were markedly affected by T_g (glass transition temperature) and T_v of the system (30–50°C higher than T_g), which turned to be functions of the composition. The composition and temperature dependence of initial polymerization rate in binary glass-forming systems were much affected by homogeneity of the polymerization system and the T_g of the glass-forming solvent. The composition and temperature dependences in the glycidyl methacrylate–triacetin system as a typical homogeneous polymerization system were studied in detail, and the polymerizations of hydroxyethyl methacrylate–triacetin and hydroxyethyl methacrylate–isoamyl acetate systems were studied for the heterogeneous polymerization systems; the former illustrates the combination of lower T_g monomer and higher T_g solvent and the latter typifies a system consisting of higher T_g monomer and lower T_g solvent. All experimental results for the composition and temperature dependence of initial polymerization rate in binary glass-forming systems could be explained by considering the product of the effect of the physical effect relating to T_v and T_g of the system and the effect of composition in normal solution polymerization at higher temperature, which was also the product of a dilution effect and a chemical or physical acceleration effect.     

Synthesis and biological evaluation of nigranoic acid esters as novel human neutrophil elastase inhibitors

Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as lung disorders and other inflammatory diseases. A series of 12 new nigranoic acid esters were regioselectively synthesised in good yields and evaluated for HNE inhibitory activity. Nigranoic acid exhibited significant inhibitory activity against HNE with the IC₅₀ value of 3.77 μM, and six esters displayed considerable inhibitory effects on HNE with IC₅₀ values in the range of 2.61–8.95 μM. The nigranoic acid esters having phenyls substituted with bromine and trimethoxyls (3h and 3b) showed stronger inhibitory activity on HNE than nigranoic acid.     

Untersuchung reversibler Photoprozesse durch Blitzlichtphotolyse IV. Triplettzustände des 1, 3, 6′, 8′- tetramethyl-dehydrodianthrons

By means of the flash photolysis technique, transient absorption spectra attributed to tetramethyl-dehydrodianthrone (TMD) in both the photochromic and triplet states have been investigated in polymethylmethacrylate matrices and in the solvent triacetin. In polymethylmethacrylate matrices and in rigid glasses of triacetin the triplet state of TMD is heavily populated. Triplet-triplet absorption and phosphorescence measurements show that below 180°K the triplet decay follows first order kinetics with the decay constant k=11,3 ± 0,1 s^?1. In incompletely solidified triacetin glass it is possible to monitor the transient absorption of the photochromic and the triplet state simultaneously. It is shown that the photochromic state ¹A₁* is not generated via the triplet state. Therefore the authors suggest a kinetic scheme characterised by a direct singlet state - photochromic state transition.     

Synthesis of o-Carboranyl Containing Esters of Pentavalent Phosphorus Acids

Abstract

A new method for the synthesis of o-carboranyl containing phosphoric, phosphonic and phosphinic acid esters, where the o-carboranil group is in the ester group, has been developed. The propargyl esters of these acids were prapared in two ways: by the reaction of phosphorus acid salts with propargyl chlorid and by interaction of propargyl alcohol with acid chlorides in the presence of Et₃N. The propargyl esters have been converted into carboranyl containing compounds upon treatment with decaborane and dimethyl aniline     

p-tert-Butyldihomooxacalix[4]arene/p-tert-Butylcalix[4]arene: Transition and Heavy Metal Cation Extraction and Transport Studies by Ketone and Ester Derivatives

The binding properties of two phenylketones (2a and 3a) and two ethylesters (2b and {3b) derived from p-tert-butyldihomooxacalix[4]arene or from p-tert-butylcalix[4]arene, in the cone conformation, towards transition (Ag⁺, Ni²⁺, Cu²⁺, Co²⁺, Zn²⁺, Fe²⁺ and Mn²⁺) and heavy (Cd²⁺, Hg²⁺ and Pb²⁺) metal cations have been determined by extraction studies with metal picrates and liquid membrane transport experiments with the same salts. The affinity of these ligands for Ag⁺ has also been investigated by ¹H NMR spectroscopy. Both ketones are better extractants than the esters, and show a strong preference for Ag⁺, while Cu²⁺ is the most extracted cation with the esters. ¹H NMR titrations with AgSO₃CF₃ indicate 1 : 1 complexes for all ligands, those with ketones are more stable, on the NMR time scale, than those with esters. Both esters are good carriers for Ag⁺, and 2b exhibits the highest transport rate (4.7 mol h^-1) found until now with dihomooxacalix[4]arene derivatives.     

Umsetzung von phosphororganischen CH-aciden Verbindungen mitSchiffschen Basen in Gegenwart saurer und basischer Katalysatoren, 7. Mitt.: Umsetzung von Estern der p-Brom-benzylphosphonsäure in Gegenwart von Natriumamid und Aluminiumchlorid

The esters of p-bromobenzylphosphonic acid (1) react withSchiff bases (2) in the presence of 0.5 mols of NaNH₂ in ether at –33° and 10° as well as in liquid ammonia to give esters of 2-arylamino-2-aryl-1-(p-bromophenyl)-ethanephosphonic acids (3 and4) in 33–78% yields. In many cases and particularly in liquid ammonia and in ether at 10° the olefin5 is formed along with the adducts3 and4. In a low extent1 a and2 a react also in the presence of AlCl₃ to form3 a in 20% yield. The stereochemistry of the reaction is studied by thin layer chromatography, and the reactivity of1 is compared with that of the esters of benzylphosphonic acid.     

Separation of Long And Short Chain Fatty Acids as Naphthacyl and Substituted Phenacyl Esters by High Performance Liquid Chromatography

Abstract

High performance liquid chromatography of various C₂ - C₂₄ fatty acids was performed with their p-bromophenacyl, p-nitrophenacyl, p-chlorophenacyl, and 2-naphthacyl esters. All separations were accomplished with two types of reversed phase columns with the eluent consisting of an acetonitrile: water gradient. For all derivatives tested, the separations were well defined and analogous, although certain esters eluted together as single peaks. Quantitative results indicate that the limit of detection in the present study is two picograms of n-caproic acid and 10 picograms of arachidonic acid as their p-bromophenacyl esters.     

Trimethylsilyl and Trimethylstannyl Esters of Trithiophosphonic Acid,Starting Compounds for the Synthesis of S-P-Heterocycles

Abstract

The silyl and stannyl esters of trithiophosphonic acids RP(S)(SEMe₃)₂ (E=Si, Sn; R=Me, t-Bu) are formed in high yield from the corresponding phosphanes RP(EMe₃)₂ by the addition of three sulfur atoms (3/8 S₈). The stannyl esters can also be obtained from the silyl esters and SnMe₃Cl or by reacting dithio=phosphonic acid anhydrides [RP(S)S]₂ with (SnMe₃)₂S. As a result of the pre=formed P-S-bonds and the reactivity of the S-E-bond towards Cl₂, Br₂ as well as chlorosulfanes S_xCl₂, the esters represent ideal starting compounds for the synthesis of sulfur-phosphorus-heterocycles of general formulas A and B. The tetrathiadiphosphorinanes [RP(S)S₂]₂, the products of the reaction with the halogens, are also formed in excellent yield when the silyl esters are treated with dimethylsulfoxide.     

Synthesis and Resolution of Dinucleotide(TpAZT) Phosphoramidates

Abstract

Dinucleotide (TpAZT) phosphoramidates were synthesized through Atherton-Todd reaction of dinucleoside H-phosphonates and amino acid methyl esters, and their diastereomers (R_p and S_p) were separated by crystallization. It was showed that the cheap methyl esters of natural alanine and phenylalanine could act as new chiral auxiliaries for large-scale synthesis of dinucleotide analogs.     

Acetylene Phosphonates as Dienophiles: A Route to Carbocyclic and Aromatic Phosphonates and Diphos-Phonates

Abstract

Systematic research of unsaturated phosphonates, started at the end of the sixties, gave rise to a variety of acetylene phosphonic derivatives. The authors worked out two significant routes to these compounds, (1) action of PCl₅ upon some alkynes followed by HCl elimination which gives alkyne dichlorophosphonates. and (2) Arbuzov reaction of P_III esters with halo- and dihaloalkynes which gives different phosphono- and diphosphonoacetylenes. The phosphonic groups are electron-withdrawing, and acetylenephosphon-ates are typical dienophiles in Diels-Alder cycloaddition of diene-donor/dienophile-acceptor type. Phosphonic esters are less active than corresponding dichlorophosphonates, but diphosphonic esters expose high reactivity. Haloethyne- and dialkylaminoethynephosphonates are sufficiently active in the reaction with simple dienes (butadiene, iso-prene, 2,3-dimethylbutadiene and piperylene), but we were not able to introduce alkyl- or arylacetylene phosphonic esters in the cycloaddition.     

The Gas-Chromatographic Behaviour of the Phosphoric Acid n-Alkyl Esters on Silicon Stationary Phases. Reactions on Columns

Abstract

Instability of the trialkylphosphates (RO)₃P(O), with R ? C₂H₁₁ - C₈H₁₇ has been observed when pairs of these esters were analysed on gas-chromatographic columns with silicone stationary phases, e.g., OV-17. New peaks were identified between those corresponding to the initial esters analysed separately. The Kovats retention indices were calculated for these peaks, with n-alkanes, as standards and phosphorus indices with tri-n-alkyl-phosphates as standards. The relationships between the retention indices and the number of the total carbon atoms in the molecules of the alkyl-phosphates was represented for the identification of the new peaks. The new peaks were identified as mixed phosphates with general structure (RO)z(RO)P(O), where R and R are alkyl radicals C₅H₁₁-C₆H₁₇. These phosphates are the results of interchange of alkoxy groups from the esters in the conditions of high temperature (240°C) of the chromatographic colums. The retention data of the esters examined are shown in the table.     

Organogelation and cytotoxic evolution of phosphonate ester functionalised hydrophobic alkanediamide motifs

Here we report various rigid alkanediamide derivatives, with three different substitution patterns of phosphonate ester for investigation of organogelation properties. The gelation properties of these compounds can be tuned by altering the number and position of the phosphonate esters. It was found that supramolecular self-assembly of the bisphosphonate esters (1a, 1d, 1h and 2a–b) resulted gel formation, whereas that of the tetraphosphonate esters (3a, 3d, 3h) resulted in construction of nanospheres and microspheres. The diverse morphology of the gel formation appears to depend predominantly on the substituted phenyl ring of the phosphonate ester functionality. Subsequent in vitro cytotoxic screening against four human tumour cell lines (A549, MDA-MB-231, MCF-7 and HeLa) using MTT assays revealed that derivatives 1f–h and 3a show cytotoxic potencies at concentrations less than 5 μM (IC₅₀ values). Compounds 1f–h exhibited promising activity against A549 cell line, 1g–h were highly effective against MDA-MB-231, 1f and 3a show potential against MCF-7 and 1f–g were active against the HeLa cell line.     

A study of homologation and the occurrence of an SA-SC-SA sequence of phases in the 4-n-alkoxy-3-fluorophenyl 4-(5-n-alkyl-2-thienyl)benzoates

Abstract

Seventeen esters, derived from 4-n-alkoxy-3-fluorophenols and 4-(5-n-alkyl-2-thienyl)benzoic acids, have been prepared and their liquid crystal transition temperatures determined by thermal optical microscopy. On cooling the isotropic liquid, the S_A-S_C-S_A sequence of phases reported for the octyloxy-octyl and octyloxy-nonyl esters has been observed for certain other homologues, principally members of the 4-(5-n-nonyl-2-thienyl)benzoates. For these compounds, the temperature range of occurrence of the intermediate S_C phase decreases as the length of the alkoxy chain increases (for the hexyloxy-nonyl to dodecyloxy-nonyl esters) and the S_c phase is absent for the tetradecyloxy-nonyl homologue.     

Smectic behaviour of methyl 4-alkoxybenzoates with a partially fluorinated alkyl chain

A series of 4-alkoxybenzoic acids 1[m,n] and their methyl esters 2[m,n] containing a partially fluorinated alkyl chain was prepared and their physical properties were investigated by optical, thermal and powder X-ray diffraction (XRD) methods. The former exhibits an SmC phase, while the latter form an SmA phase. XRD analysis indicated liquid-like character of the linking alkyl chains, and showed a decreasing layer thermal expansion coefficient from positive to negative upon increasing the degree of fluorination. The new esters 2[m,n] expanded the series and permitted analysis of trends in thermal stability of the SmA phase. The results demonstrate that the SmA–I transition temperature increases by about +20 K per CF₂CF₂ unit, and is destabilised by –5.6 K upon extending the hydrocarbon part by each CH₂CH₂ group. Data for the expanded series 2[m,n] were used for comparative analysis of mesogenic behaviour in two other series of derivatives of 1[m,n]. Synthetic methods for 1[m,n] and 2[m,n] are reviewed.     

Poly-α-n-alkyl Acrylic Derivatives: Synthesis,Influence of Molecuur Weight and n-Alkyl Group Length on Physical and Physicochemical Properties

Abstract

A series of α-n-alkyl acrylic acid monomers was synthesized and homopolymerized by a radical route. Methylation of polyacids using diazomethane led to the corresponding methyl esters and allowed physicochemical analysis. The thermal stability of polyacids and polymethyl esters is insensitive to the nature of the alkyl group and to the molecular weight. The glass transition temperature, T _g, classically decreases with increases in alkyl group length such as alkyl polymethacrylates. Molecular weight has a drastic influence on T _g for short alkyl groups.     

Reductive Amination of Glycosyl Aldoses: Synthesis of N‐Glycosylated β‐Glycosyl Amino Alcohols and their Enzyme Inhibitory Effect

Abstract

Reductive amination of glycosyl aldehydes (1a–c, 2) with glycosyl amino esters (3a–c, 4) in the presence of sodium borohydride gave diglycosylated amino esters (5–15) in good yield. N‐Glycosyl‐glycosylated amino esters were reduced to the respective diglycosyl amino alcohols (16–26) with LiAlH₄ in good yield. All the synthesized compounds were studied for their inhibitory effect, if any, against hepatic glucose‐6‐phosphatase, glycogen phosphorylase, and intestinal brush border membrane α‐glucosidase; among these compounds 7, 21, and 25 have shown marked inhibition on these enzymes, respectively.     

Anti- and prooxidant activity of triphenylantimony(V) catecholates derived from alkyl gallates

Antiradical and antiand prooxidant activities of the newly obtained triphenylantimony(V) catecholate complexes derived from gallic acid esters of the general formulas (RO(O)C–Cat)SbPh₃ (R = Me (1), C₈H₁₇ (2), C₁₂H₂₅ (3)) and (MeO(O)C–(OH?NEt₃)Cat)SbPh₃ (4) were studied. The comparative study involving gallic acid esters of the general formula RO(O)C–GallH₃ (R = Me (5), C₈H₁₇ (6), C₁₂H₂₅ (7)) was performed in order to evaluate the effect of organic ligands on the properties of the antimony(V) compounds. The values of EC50, the number of converted molecules of stable radical (nDPPH), as well as the relative content of oleic acid hydroperoxides confirm the antiradical and antioxidant activity of triphenylantimony(V) complexes in reactions with diphenylpicrylhydrazyl radicals and in the antioxidation of oleic acid. The influence of more active compounds 1 and 4 and ester 5 on lipid peroxidation of the rat liver homogenate of male Wistar line was determined. The membraneprotective properties were evaluated for induced hemolysis of erred blood cells as an example, and catalase activity of erythrocyte hemolysate was studied.