Aldonamide-type gemini surfactants: Synthesis, structural analysis, and biological properties

A new group of nonionics, so-called sugar surfactants having a gemini structure, N,N′-bisalkyl-N,N′-bis[(3-gluconylamido)propyl]ethylenediamines [bis(C _n GA): C _n =n-C₈H₁₇, n-C₁₂H₂₅], N,N′-bisdodecyl-N,N′-bis[(3-glucoheptonylamido)propyl]ethylenediamine [bis(C₁₂GH)], and N,N′-bisalkyl-N,N′-bis[(3-lactobionylamido)propyl]ethylenediamines [bis(C _n LA): C _n =n-C₈H₁₇, n-C₁₂H₂₅], were prepared in a convenient four-step procedure from easily accessible reagents. Their structure and purity were confirmed by means of elemental analysis, electrospray ionization MS (ESI-MS), and NMR spectra—¹H, ¹³C, ¹H−¹³C COSY, and distortionless enhancement by polarization transfer. All tested surfactants were practically nontoxic to gram-negative bacteria and fungi, but they inhibited the growth of some gram-positive bacteria. From the results of the Closed Bottle test (OECD Guideline 301D) for biodegradability measurements, it was concluded that the tested aldonamide gemini structures are biodegraded by environmental microorganisms to 16–55% of the initial levels by day 28, the extent depending on both the aldonamide type and the alkyl chain length. Consequently, N,N′-bisalkyl-N,N′-bis[(3-aldonylamido)propyl]ethylenediamines are a surfactant class having low ecotoxicity and fulfilling requirements desired from an ecological standpoint.     

Synthesis and surface properties of N-dodecyl-N,N-bis[3-(aldonamido)propyl]amine-N-oxides

A new group of saccharide surfactants, N-dodecyl-N,N-bis[3-(aldonamido)propyl]amine-N-oxides (derivatives of d-gluconic, d-glucoheptonic, and lactobionic acids), were synthesized with high yields by one-step oxidation reaction of an appropriate N-dodecyl-N,N-bis[3-(aldonamido)-propyl]amine with an excess of 30 wt% of an aqueous solution of hydrogen peroxide. Their structures and purity were confirmed by means of elemental analysis, electrospray ionization mass spectrometry, and ¹H and ¹³C nuclear magnetic resonance spectroscopy. In comparison to an appropriate N-dodecyl-N,N-bis[3-(aldonamido)propyl]amine, the investigated N-oxides are more soluble in water with similar critical micelle concentration values and show higher surface effectiveness. They are low-foamable but in mixtures with sodium dodecyl sulfate form high-volume and stable foams in a wide range of mixture compositions.     

Synthesis and Properties of 1,1-bis{[3-(<Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-Dimethylamino)propyl]amido}alkane-di-<Emphasis Type="Italic">N</Emphasis>-oxides

A homologous series of new surface-active 1,1-bis{[3-(N,N-dimethylamino)propyl]amido}alkane-di-N-oxides were synthesized in the reaction of an appropriate diethyl 2-alkylmalonate with N,N-dimethylamino-1,3-propanediamine followed by oxidation with aqueous hydrogen peroxide. The adsorption isotherms of their aqueous solutions were measured and evaluated to obtain adsorption parameters: critical micelle concentration (CMC), surface excess concentration (Γ_CMC), equilibrium surface tension at the CMC (γ_CMC), cross-sectional area of the adsorbed surfactant molecule (A _CMC), efficiency of surface adsorption (pC₂₀), standard free energies of adsorption (ΔG°_ads), and micellization (ΔG°_CMC). All investigated di-amidoamines and di-N-oxides were practically non-toxic to selected bacteria and yeasts. These compounds are readily biodegradable in the Closed Bottle Test inoculated with activated sludge. Surface and biological properties showed that this group of N-oxide-type compounds has high surface activity and fulfills requirements for environmental acceptance.

Synthesis and Surface Properties of Dicephalic Surfactants with a 1,3-Dioxane Ring

A new group of surface active dicephalic derivatives of 1,3-dioxane, i.e., 2-alkyl-5,5-bis{[3-(N,N-dimethylamino)propyl]amido}-1,3-dioxane-di-N-oxides, were synthesized with high yields by the reaction of an appropriate 2-alkyl-5,5-bis-(carboxyethyl)-1,3-dioxane with an excess of N,N-dimethyl-1,3-propanediamine followed by oxidation with an aqueous solution of hydrogen peroxide. Structures and purity of all intermediates and final di-N-oxides were confirmed by means of ¹H-NMR and ESI-MS spectroscopy. Synthesized compounds showed high surface activity with low values of critical micelle concentration and high effectiveness of surface tension reduction (γ _CMC). However, only derivative with the longest 2-alkyl substituent showed good foaming and moderate emulsifying properties.

A novel ∈-lysine acylase from <Emphasis Type="Italic">Streptomyces mobaraensis</Emphasis> for synthesis of <Emphasis Type="Italic">N∈</Emphasis>-acyl-<Emphasis Type="SmallCaps">l</Emphasis>-lysines

A novel ∈-lysine acylase (N ₆-acyl-l-lysine amidohydrolase; EC 3.5.1.17) was isolated from Streptomyces mobaraensis and purified to homogeneity by SDS-PAGE from the culture broth. The purified enzyme was monomeric, with a molecular mass of approximately 60 kDa. The enzyme was inactivated by the presence of 1,10-phenanthroline and activated in the presence of Co²⁺ and Zn²⁺. The enzyme showed a pH optimum of 8.0 and was stable at temperatures of up to 50°C for 1 h at pH 8.0. The enzyme specifically catalyzed the hydrolysis of the amide bond of various N∈-acyl-l-lysines. Furthermore, the enzyme efficiently catalyzed the synthesis of N∈-acyl-l-lysines with fatty and aromatic acyl groups in an aqueous buffer. In the syntheses of N∈-decanoyl-l-lysine, N∈-lauroyl-l-lysine, and N∈-myristoyl-l-lysine, the product precipitated and the yield was 90% or higher using 10 mM FA and 0.5 M l-lysine as the substrate.     

Lipase-Catalyzed Synthesis of d-Psicose Fatty Acid Diesters and their Emulsification Activities

The diesterification of d-psicose (the C-3 epimer of d-fructose) with fatty acid vinyl esters of selected acyl chain lengths (C₈, C₁₀, and C₁₂) was successfully carried out using Candida antarctica lipase (Novozym 435) at 45 °C for 24 h to give the 1,6-diacyl-d-psicofuranoses with a high regioselectivity in good yields (83–90%). These diesters of d-psicose have hydrophilic-lipophilic balance (HLB) values (6.5–8.2) similar to HLB values of monoglyceride compounds which constitute the largest single type of emulsifiers employed by the food industry. Ability of the d-psicose diesters to stabilize oil-in-water emulsions and the weight-averaged oil-droplet diameter in the emulsions was evaluated in this study. Emulsion stability of oil droplets stabilized by d-psicose dicaprylate (0.3%, w/v in oil phase) was comparable to d-fructose dicaprylate (0.2%, w/v). It was further confirmed that the d-psicose diesters exhibited an emulsification activity depending on the chain length of fatty acid; d-psicose dicaprate showed better emulsion stability than the other diesters.     

Preparation and properties of new surfactants containingd-glucosamine as the building block

Three types of new surfactants were prepared by usingN-acetyl-d-glucosamine as a starting material. The first type of surfactant, sodium methyl 4,6-O-alkylidene-2-(carboxyl-atomethylamino)-2-deoxy-d-glucopyranoside, was prepared successively by the following treatments: methyl glucosidation ofN-acetyl-d-glucosamine, transacetalization with an appropriate aldehyde dimethyl acetal, deacetylation, and finally reaction of the resulting methyl-4,6-O-alkylidene-2-amino-2-deoxy-d-glucopyranoside (2-amino precursor) with bromoacetic acid. The reaction of this 2-amino precursor with methyl iodide yielded the second type of surfactant, methyl 4,6-O-alkylidene-2-deoxy-2-(trimethylammonio)-d-glucopyranoside iodide, in excellent yield. The last type of compound, sodium methyl 2-acetamide-4,6-O-alkylidene-3-O-[1-(carboxylato)-ethyl]-2-deoxy-d-glucopyranoside, was synthesized by the reaction of methyl 2-acetamide-4,6-O-alkylidene-2-deoxy-d-glucopyranoside with 2-chloropropionic acid. Concerning the two carboxylate types of surfactants, the compounds containing a C₉ or C₁₁ hydrophobic chain in the alkylidene part showed higher water solubility than the corresponding compounds containing a C₇ hydrophobic chain. Both the micelle-forming property and the ability to lower the surface tension of these carboxylate types of compounds increased with an increase in the length of the hydrophobic chain in the alkylidene part. These compounds can be applied to new acid-decomposable types of cleavable surfactants because they contain an acetal group. The acetal bond of the ammonium type of compound was cleaved more slowly than that of the corresponding carboxylate types of surfactants in 2% aqueous HCI solution. The biodegradabilities of these compounds were also determined.     

Novel glucose-derived gemini surfactants with a 1,1′-ethylenebisurea spacer: Preparation, thermotropic behavior, and biological properties

In the search for environmentally safe surfactants made from inexpensive and renewable sources, the interest has mainly been focused on new saccharide derivatives. This report describes the synthesis of newly designed nonionic gemini compounds comprising two reduced sugar headgroups, two alkyl tails, and a 1,1′-ethylenebisurea entity as the spacer linking two amphiphilic glucose-derived moieties. Thus, the series of N,N′-bis[(3-alkyl-3-deoxy-d-glucitol)ureido]ethylenediamines (bis(C_nGT), with C_n=n-C₉H₉, n-C₆-H₁₃, n-C₈H₁₇, n-C₁₀H₂₁, or n-C₁₂H₂₅), were prepared using a convenient procedure starting from easily accessible reagents such as d-glucose, n-alkylamines, urea, and ethylenediamine. Their structure and purity were confirmed by means of elemental analysis, electrospray ionization mass spectrometry, and ¹H and ¹³C nuclear magnetic resonance spectroscopy. Additionally, the present contribution introduces selected properties of these surfactants, including their thermotropic behavior and biological properties. The presence of two phase transition points, determined using the differential scanning calorimetry method, indicates liquid-crystalline mesophase formation upon heating. Furthermore, using the closed-bottle test (OECD Guideline 301D) as well as the biological oxygen demand test for insoluble substances for biodegradability measurements, it has been concluded that the tested glucose-derived gemini structures achieve more than 60% biodegradation after 64–75 test days. All tested surfactants were practically nontoxic to bacteria, yeast, and molds. Owing to their fitting aggregation ability as well as their nontoxicity, they constitute an interesting group of surfactants for various applications.     

Self-Assembly of Metalloporphyrin-L-Cysteine Modified Gold Electrode

A novel composite film containing metalloporphyrins was fabricated by in situ electrochemical scanning on an L-cysteine self-assembled monolayer modified gold electrode. SEM and ATR-FTIR were used to characterize the structure of the film. The electrochemical properties were investigated through techniques such as a.c. impedance, cyclic voltammetry and chronocoulometry. The porphyrin-L-cysteine film showed no peak in the first cycle, while each of the composite films derived from three different metalloporphyrin-L-cysteines presented a pair of reversible redox peaks in 1.0 mol L^–1 H₂SO₄. These peaks correspond to the rapid redox process of the metal. The supporting electrolyte and its pH value influenced the stability and sensitivity of the composite film. Cupric-porphyrin-L-cysteine film showed good catalytic activity for the reduction of H₂O₂. The catalytic current was linear to H₂O₂ concentration in the range 1.0 × 10^–6 to 3.0 × 10^–5 mol L^–1, with a correlation coefficient of 0.9995. The detection limit was 1.0 × 10^–7 mol L^–1 at a signal to noise ratio of 3. The relative standard deviation was calculated as 2.4% for solutions containing 1.0 × 10^–5 mol L^–1 H₂O₂(n= 11).     

Bifunctional N-Oxides of Alkyldiamidoamines

A homologous series of new surface-active 1,1-bis{[3-(N,N-dimethylamino)ethyl]-amido}alkane-di-N-oxides were synthesized in the reaction of an appropriate diethyl 2-alkylmalonate with N,N-dimethylethylenediamine followed by oxidation with an aqueous solution of hydrogen peroxide. The adsorption isotherms of their aqueous solutions were measured and evaluated to obtain adsorption parameters: critical micelle concentration (CMC), surface excess concentration (Γ_CMC), equilibrium surface tension at the CMC (γ _CMC), cross-sectional area of the adsorbed surfactant molecule (A _CMC), standard free energies of adsorption and micellization

Enzymatic synthesis of N-acyl-l-amino acids in a glycerol-water system using acylase I from pig kidney

N-Medium- and long-chain acyl-l-amino acids were enzymatically synthesized from the corresponding l-amino acids and fatty acids using a reverse hydrolysis. Enzymes that are suitable for the synthetic reaction of N-acyl-l-amino acids were screened on the basis of hydrolytic activity toward N-lauroyl-l-glutamic acid as an indicator. Acylase I from pig kidney (EC 3.5.1.14) showed the highest N-acyl-l-amino acid hydrolytic activity among 57 commercially available enzymes tested. Acylase I effectively catalyzed the synthesis of N-lauroyl-l-amino acids except for N-lauroyl-l-proline and N-lauroyl-l-tyrosine in a glycerol-water system. Under the optimized reaction conditions, N-lauroyl-l-arginine and N-lauroyl-l-glutamic acid were obtained in conversions of 82 and 44%, respectively. The equilibrium constants calculated from the conversion obtained were 5.6, 15.4, 18.0, and 39.4 for the syntheses of N-lauroyl-l-glutamic acid, N_α-lauroyl-l-lysine, N-lauroyl-l-glutamine, and N-lauroyl-l-methionine, respectively. N-Acyl-l-arginines with myristic acid and palmitic acid as the fatty acid were also synthesized using acylase I.     

Enantiospecific synthesis fromd-fructose of (2S,5R)- and (2R,5R)-2-methyl-1,6-dioxaspiro[4.5]decane [the odor bouquet minor components ofParavespula vulgaris (L.)]

The synthesis of (2S,5R)-(1) and (2R,5R)-2-methyl-1,6-dioxaspiro [4.5]decane (2) from (2RS,5R,8R,9R,10S)-8,9,10-trihydroxy-2-methyl-1, 6-dioxaspiro[4.5]decane (8), obtained in five steps fromd-fructose using Wittig's methodology, reduction, and spiroketalation, has been accomplished by a Corey dideoxygenation at C-8,9, followed by a Barton deoxygenation at C-10, of the appropriately protected derivatives.Enantiospecific synthesis of spirocetals. Part V. For Part IV, see Izquierdo et al. (1992).     

Biocatalytic synthesis of some chiral drug intermediates by oxidoreductases

Chiral intermediates were prepared by biocatalytic processes with oxidoreductases for the chemical synthesis of some pharmaceutical drug candidates. These include: (i) the microbial reduction of 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanone (1) to R-(+)-1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanol (2) [R-(+)-BMY 14802], an antipsychotic agent; (ii) the reduction of N-4-(1-oxo-2-chloroacetyl ethyl) phenyl methane sulfonamide (3) to the corresponding chiral alcohol (4), an intermediate for d-(+)-N-4-{1-hydroxy-2-[(-methylethyl)amino]ethyl}phenyl methanesulfonamide [d-(+) sotalol], a β-blocker with class III antiarrhythmic properties; (iii) biotransformation of Nɛ-carbobenzoxy (CBZ)-l-lysine (7) to Nɛ-CBZ-l-oxylysine (5), an intermediate needed for synthesis of (S)-1-[6-amino-2-{[hydroxy(4-phenylbutyl)phosphinyl]oxy}1-oxohexyl]-l-proline (ceronapril), a new angiotensin converting enzyme inhibitor (6) and (iv) enzymatic synthesis of l-β-hydroxyvaline (9) from α-keto-β-hydroxyisovalerate (16). l-β-Hydroxyvaline (9) is a key chiral intermediate needed for the synthesis of S-(Z)-{[1-(2-amino-4-thiazolyl)-2-{[2,2-dimethyl-4-oxo-1-(sulfooxy)-3-azetidinyl] amino}-2-oxoethylidene]amino}oxyacetic acid (tigemonam) (10), an orally active monobactam.     

Synthesis and surface properties of chemodegradable anionic surfactants: Diastereomeric (2-n-alkyl-1,3-dioxan-5-yl) sulfates with monovalent counter-ions

Sodium, potassium and ammonium cis- and trans-(2-n-alkyl-1,3-dioxan-5-yl) sulfates 6–8 (alkyl: n-C₉H₁₉, 6a–8a, and n-C₁₁H₂₃, 6b–8b) were synthesized in a reaction of aliphatic aldehydes 1a,b with glycerol 2 followed by separation in high yields of individual geometric isomers of cis-and trans-2-n-alkyl-5-hydroxy-1,3-dioxanes, cis-3a,b and trans-3a,b, followed by sulfation with sulfur trioxide-pyridine complex, and finally neutralization with NaOH, KOH, and NH₄OH, respectively. Physical data of the compounds and some surface properties of 2-n-nonyl derivatives, such as critical micelle concentration (CMC), effectiveness of aqueous surface tension reduction (Π_CMC), surface excess concentration Γ_CMC, and the surface area demand per molecule (A_CMC), were determined. It was shown that the surface activity of these compounds is influenced both by their geometric structure and by the monovalent counter-ion.     

Direct <Emphasis Type="SmallCaps">d</Emphasis>-Glucose Oxidation over Noble Metal Nanoparticles Introduced on Polymer and Inorganic Supports

In the present work, nanocatalysts prepared on inorganic supports (zeolites) were investigated in d-glucose oxidation and compared to systems supported on polymer (hypercrosslinked polystyrene (HPS)) previously described. Catalytic activities and selectivities were measured under various reaction conditions. The selectivity of d-glucose oxidation and activity of both Pd-containing zeolites and HPS-Ru were similar (99.7% and TOF 0.013–0.014 mol/(mol Me s)). Physicochemical analysis X-ray photoelectron spectroscopy, liquid nitrogen physisorption, diffuse reflectance infrared Fourier transform spectroscopy of adsorbed CO for metal sites evaluation, CD₃CN for acid sites evaluation showed that Pd species were in oxidic form, while Ru species were in oxidic and reduced form. The catalytic activity decreased when acidic sites were present in Pd-containing zeolites.     

Osmium(VIII)/Ruthenium(III) Catalysed Oxidation of l-lysine by Diperiodatocuprate(III) in Aqueous Alkaline Medium: A Comparative Mechanistic Approach by Stopped Flow Technique

Abstract The kinetics of osmium(VIII) and ruthenium(III) catalysed oxidation of l-lysine (l-lys) by diperiodatocuprate(III) (DPC) in alkaline medium at a constant ionic strength of 0.15 mol dm⁻³ was studied spectrophotometrically. The reaction between l-lys and DPC in alkaline medium exhibits 1:2 stoichiometry in both catalysed reaction (l-lys: DPC). The reaction is first order in [DPC] and has less than unit order both in [l-lys] and [alkali]. Increase in periodate concentration decreases the rate. Intervention of free radicals was observed in the reaction. The main products were identified by spot test, IR and GC-MS studies. Probable mechanisms are proposed and discussed. The reaction constants involved in the different steps of the mechanism are calculated. The activation parameters with respect to the slow step of the mechanism are computed and discussed and thermodynamic quantities are also determined. It has been observed that the catalytic efficiency for the present reaction is in the order of Os(VIII) > Ru(III). The active species of catalyst and oxidant have been identified. Graphical Abstract The kinetic and mechanistic investigations of the reaction between DPC and l-lysine has been studied in presence of microamounts of ruthenium(III) and osmium(VIII) in alkaline medium. The monoperiodatoargentate(III), [Ru(H₂O)₅OH]²⁺ and [OsO₄(OH)₂]²⁻ are considered as the active species of oxidant, DPC, ruthenium(III) and osmium(VIII) respectively.      

An Interesting Complex: [Cd(l -trp) (d-trp)] n

A novel coordination polymer [Cd(l-trp) (d-trp)] _n (where l-trp and d-trp are l-tryptophan and d-tryptophan or (S)-2-amino-3-(3-indolyl)propionic acid and (R)-2-amino-3-(3-indolyl)propionic acid) was prepared by a solvent-thermal method and characterized by elemental analysis, IR spectra and single-crystal X-ray diffraction. The compound(monoclinic space group P2(1)/c with a = 19.759(2) Å, b = 5.2496(10) Å, c = 9.7594(16) Å, β = 97.2760(10)°, Z = 2) shows a two-dimensional plane structure. The crystallized coordination polymer has a centrosymmetric space group. Each Cd²⁺ ion coordinates with a pair of racemes, and the complex is a mesomer. Although l-trp was used, both l-trp and d-trp appear in the complex.     

Study on Copper-based Catalysts for Synthesis of N,N′-bis(1,4-dimethylpentyl)-p-phenylenediamine from Reductive Alkylation of p-Nitroaniline with 5-Methyl-2-hexanone

The reductive alkylation of p-nitroaniline with 5-methyl-2-hexanone over copper-based catalysts was investigated. Furthermore, the catalysts were characterized using the techniques of XRD, H₂–N₂O titration, H₂-TPR, NH₃-TPD and pyridine-FTIR. The results showed that the addition of Mn, Ba and La into Cu–SiO₂ catalyst played an important role in the improvement of the selectivity towards N,N′-bis(1,4-dimethylpentyl)-p-phenylenediamine (BMPPD). The highest selectivity towards BMPPD over 58CuO–9MnO₂–BaO–1La₂O₃–30SiO₂ (wt.%) catalyst could be ascribed to the best dispersion of copper (i.e., the highest hydrogenation ability) and the most amounts of the surface Lewis acidic sites.     

Sex Pheromone of the Scarab Beetle <Emphasis Type="Italic">Phyllophaga</Emphasis> (<Emphasis Type="Italic">Phytalus) georgiana</Emphasis> (Horn)

The sex pheromone of Phyllophaga (Phytalus) georgiana was characterized as valine methyl ester, tentatively the l-enantiomer. This is the first sex pheromone identified from the Phyllophaga subgenus Phytalus. The pheromone was extracted from female glands, the active component isolated by coupled gas chromatography–electroantennogram detection analysis, characterized by mass spectrometry, and shown to be active in field tests. The seasonal flight pattern was determined for P. georgiana as well as for three other species, P. anxia (both northern and southern genitalic forms), P. gracilis, and P. postrema. The latter three species were captured in traps baited with l-isoleucine methyl ester. Sridhar Polavarapu, deceased May 7, 2004. We dedicate this publication to our friend and colleague.     

Biocatalytic synthesis of chiral intermediates for antiviral and antihypertensive drugs

The chiral intermediate (1S,2R) [3-chloro-2-hydroxy-1-(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 2a was prepared for the total synthesis of a human immunodeficiency virus protease inhibitor, BMS-186318. The stereoselective reduction of (1S) [3-chloro-2-oxo-1(phenylmethyl)propyl] carbamic acid, 1,1-dimethylethyl ester 1 was carried out using microbial cultures, among which Streptomyces nodosus SC 13149 efficiently reduced 1 to 2a. A reaction yield of 80%, enantiomeric excess (e.e.) of 99.8%, and diastereomeric purity of 99% were obtained for chiral alcohol 2a. Chiral l-6-hydroxy norleucine 3, an intermediate in the synthesis of antihypertensive drug, was prepared by reductive amination of 2-keto-6-hydroxyhexanoic acid 4 using beef liver glutamate dehydrogenase. The cofactor NADH required for this reaction was regenerated using glucose dehydrogenase from Bacillus sp. A reaction yield of 80% and e.e. of 99.5% were obtained for l-6-hydroxynorleucine 3. To avoid the lengthy chemical synthesis of the ketoacid, a second route was developed in which racemic 6-hydroxynorleucine [readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin 5] was treated with d-amino acid oxidase from Trigonopsis variabilis to selectively convert the d-isomer of racemic 6-hydroxynorleucine to 2-keto-6-hydroxyhexanoic acid 4 and l-6-hydroxynorleucine 3. Subsequently, the 2-keto-6-hydroxyhexanoic acid 4 was converted to l-6-hydroxynorleucine by reductive amination using glutamate dehydrogenase. A reaction yield of 98% and an e.e. of 99.5% were obtained.