Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres by organocopper reagents and application to conformationally restricted cyclic RGD peptidomimetics

Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres corresponding to dipeptides having one N-methylamino acid, and application to bioactive peptides, are described. In a key reaction introducing the chiral alpha-alkyl group of the isosteres, organocopper-mediated alkylation of syn-beta-methylated gamma-mesyloxy-alpha,beta-enoate 26a afforded E- and Z-isomers of anti-S(N)2' products in a solvent-dependent manner. The resulting two isosteres, D-Phe-psi[(E)-CH=CMe]-L-Val 27a and D-Phe-psi[(Z)-CH=CMe]-L-Val 28b, which corresponded to trans- and cis-conformers of D-Phe-L-MeVal, respectively, were utilized in a structure-activity relationship study on cyclic RGD peptides 1 and 2, in company with a psi[(E)-CH=CH]-type alkene dipeptide isostere, D-Phe-psi[(E)-CH=CH]-L-Val. The cyclic isostere-containing pseudopeptides 3, 4, and 40 were synthesized and biological activity against integrin alpha(V)beta(3) and alpha(IIb)beta(3) receptors were also evaluated.     

Tricyclic-isoxazolidine analogues via intramolecular 1,3-dipolar cycloaddition reactions of nitrones

The tricyclic-isoxazolidine analogues tetrahydrothiochromenoisoxazoles, hexahydroisoxazolequinolines and tetrahydroisoxazolepyranopyridines were prepared by an intramolecular 1,3-dipolar cycloaddition reaction of a nitrone with an alkene. For N-alkylated hexahydroisoxazolequinolines, reduction of the reaction time from two days to 40 min was achieved using microwave heating. The cyclization to form tetrahydroisoxazolepyranopyridines only proceeded when the alkene was substituted with an electron withdrawing group.     

Direct observation of insertion events at rac-(C2H4(1-indenyl)2)Zr(MeB(C6F5)3)-polymeryl intermediates: distinction between continuous and intermittent propagation modes

The propagating species for 1-hexene, propene, and ethene polymerization as catalyzed by [rac-(C2H4(1-indenyl)2)Zr(CH3)][CH3B(C6F5)3] has been intercepted at T < -40 degrees C and characterized by NMR methods. Observation of the propagating species permits direct monitoring of initiation, propagation, and termination processes by NMR. Detailed examination of alkene incorporation into Zr-polymeryl species using 13C-labeled 1-alkenes supports a continuous insertion mechanism whereby the anion re-coordinates after each alkene insertion.     

Microwave Induced 1,3-Depolar Cycloaddition Reactions of Nitrones

1,3-Dipolar cycloaddition reactions involving unreactive nitrones have been carried out successfully under microwave irradiations. The reaction of nitrones 1 and alkene 2 proceeded regiospecifically at atmospheric pressure and the corresponding isoxazolidines 3 were obtained in high yields.     

Investigation of the species-specific degradation behaviour of methylmercury and ethylmercury under microwave irradiation

The degradation behaviour of methylmercury (MeHg) under microwave irradiation is investigated, as is the (different) degradation behaviour of ethylmercury (EtHg) under similar irradiation. A simple and highly sensitive SPME-GC-pyrolysis-AFS system was used to analyse the aqueous MeHg and EtHg standard solutions after derivatization with sodium tetraphenylborate (NaBPh₄). Samples were irradiated in a microwave digester at microwave powers ranging from 20 to 160 W for durations of 2 to 10 min. The different tolerances towards microwave treatment of the two organomercury species were evident. Practically no degradation was experienced for MeHg for up to 8 minutes of irradiation at 120 W or for up to 4 minutes at 160 W. Significant analyte loss was observed for EtHg after 2 minutes at 40 W of microwave power. Awarded a Poster Prize on the occasion of the European Winter Conference on Plasma Spectrochemistry, February 2005, Budapest, Hungary     

Microwave plasma treatment of polymer surface for irreversible sealing of microfluidic devices

Microwave plasma was generated in a glass bottle containing 2-3 Torr of oxygen for plasma treatment of a polymer surface. A "kitchen microwave oven" and a dedicated microwave digestion oven were used as the power source. Poly(dimethylsiloxane)(PDMS) slabs treated by a 30 W plasma for 30-60 s sealed irreversibly to form microfluidic devices that can sustain solution flow of an applied pressure of 42 psi without leaking. Experimental set up and conditions for the production of a homogeneous plasma to activate the PDMS surface for irreversible sealing are described in detail. The surface of a microwave plasma-treated PDMS slab was characterized using atomic force microscopy (AFM) and attenuated total reflection-Fourier Transform infrared spectroscopy (ATR-FTIR). The plasma-treated surface bears silica characteristics.     

Ring-rearrangement metathesis of nitroso Diels-Alder cycloadducts

Strained nitroso Diels–Alder bicyclo[2.2.1] or [2.2.2] adducts functionalized with alkene side chains of diverse length undergo a ring‐rearrangement metathesis process with external alkenes and Grubbs II or Hoveyda–Grubbs II ruthenium catalysts, under microwave irradiation or classical heating, to deliver cis‐fused bicycles of various ring sizes, which contain a N? O bond. These scaffolds are of synthetic relevance for the generation of molecular diversity and to the total synthesis of alkaloids. The observation of unexpected reactions, such as epimerization or one‐carbon homologation of the alkene side chain, is also reported.     

Comparison of methods for extraction of tobacco alkaloids

Ultrasound and microwave techniques were used to extract tobacco alkaloids, and response surface methodology was used to optimize extraction conditions. Ultrasonic technique factors were temperature, 30-85 degrees C; time, 3-45 min; solvent volume, 8-80 mL. Microwave extraction factors were pressure, 15-75 psi; time, 3-40 min; power, 30-90% of the maximum magnetron power of 650 W. Soxhlet and solvent AOAC-modified extraction methods were also applied after some improvements. Nicotine, nornicotine, anabasine, and anatabine were quantified by gas chromatography. A steam distillation International Standards Organization method for total alkaloid evaluation was used as reference. The results obtained by the different methods were compared using a least squares deviation test. The ultrasonic and the proposed modified-AOAC extraction method were the more convenient with regard to practicability and precision. The relative deviations (n = 5) were as follows: For the ultrasonic method in low-level alkaloid tobaccos, 0.7% nicotine and 1.4-14% minor alkaloids; in high-level alkaloid tobaccos, 2.4% nicotine and 4.5-5.1% minor alkaloids. For the modified AOAC method in low-level alkaloid tobaccos, 0.9% nicotine and 2.4-11.6% minor alkaloids; and in high-level alkaloid tobaccos, 1.7% nicotine and 2.0-2.4% minor alkaloids.     

Electric Potential (psi(delta) and psi(d)) at Outer Helmholtz Plane and Midplane on the Clay Colloid Surface with Overlapping Flat Double Layers

An anion negative adsorption equation in the condensed colloidal suspension with overlapping flat double layers was derived according to Gouy-Chapman theory. The electric potential at the outer Helmholtz plane (OHP), psi(delta), and the electric potential at the midplane, psi(d), were numerically solved by computer using the anion negative adsorption equation on the basis of experiments. The results showed that psi(delta) and psi(d) increase with the decrease of the distance between two clay plates, lambda, at first in the given electrolyte concentration. When lambda is smaller than 50-70 ?, psi(d) remains almost unchanged while psi(delta) declines remarkably with the further decrease of lambda. The change of psi(d)/psi(delta) with lambda can explain and manifest overlapping degree of flat double layers more appropriately than psi(d) in previous works. Due to compression of the flat double layer on the clay colloid surface at increasing electrolyte concentration, the magnitude of the electrical potentials at OHP and midplane is considerably reduced at a given lambda. Copyright 2000 Academic Press.     

Codimerization and carbonylation of normal alkenes and isobutylene

Conclusions An equimolar mixture of a normal (or cyclic) alkene and an alkene with a branch at the double bond (or a tertiary alcohol) in the presence of the BF₃·H₂O -liquid-SO₂ catalytic system under 1 atm of CO at a temperature of –30 to –40°C undergoes selective codimerization followed by carbonylation and the formation of codimeric carboxylic acids with 70 to 93% yields.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1057–1063, May, 1978.     

Microwave-mediated Claisen rearrangement followed by phenol oxidation: a simple route to naturally occurring 1,4-benzoquinones. The first syntheses of verapliquinones A and B and panicein A

The naturally occurring 1,4-benzoquinones 2-methoxy-6-propyl-1,4-benzoquinone (1), 2-methoxy-6-pentyl-1,4-benzoquinone (primin 2), 2-methoxy-6-pentadecyl-1,4-benzoquinone (3), 2-methoxy-6-heptadecyl-1,4-benzoquinone (dihydroirisquinone, pallasone B; 4) were synthesized by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 10, followed by hydrogenation of the side chain alkene, and oxidation to the quinone. The Claisen-based methodology was extended to the first synthesis of the marine benzoquinones verapliquinones A and B (5 and 6), and panicein A (7). Isoarnebifuranone (9) was also synthesized by a similar strategy.     

A nearly isosteric photosensitive amide-backbone substitution allows enzyme activity switching in ribonuclease s

psi[CS-NH]4-RNase S, a site specific modified version of RNase S obtained by thioxylation (O/S exchange) at the Ala4-Ala5- peptide bond, was used to evaluate the impact of protein backbone photoswitching on bioactivity. psi[CS-NH](4)-RNase S was yielded by recombination of the S-protein and the respective chemically synthesized thioxylated S-peptide derivative. Comparison with RNase S revealed similar thermodynamic stability of the complex and an unperturbed enzymatic activity toward cytidine 2',3'-cyclic monophosphate (cCMP). Reversible photoisomerization with a highly increased cis/trans isomer ratio of the thioxopeptide bond of psi[CS-NH](4)-RNase S in the photostationary state occurred under UV irradiation conditions (254 nm). The slow thermal reisomerization (t(1/2) = 180 s) permitted us to determine the enzymatic activity of cis psi[CS-NH](4)-RNase S by measurement of initial rates of cCMP hydrolysis. Despite thermodynamic stability of cis psi[CS-NH](4)-RNase S, its enzymatic activity is completely abolished but recovers after reisomerization. We conclude that the thioxopeptide bond modified polypeptide backbone represents a versatile probe for site-directed photoswitching of proteins.     

Thermosetting polyimides

Linear polyimides prepared from m-phenylene diamine (MPD) and 3,4,3′,4′-benzophenonetetracarboxylic dianhydride (BTDA) were modified so as to be thermosetting. This was done by replacing a portion of the MPD with either 2,4-diaminoacetanilide or p-(2,4-diaminophenoxy) acetanilide and 3,5-diaminobenzoic acid; it is thought that during final processing of the laminates the carboxyl group and the acetamido group react, forming amide crosslinks. Alternatively, excess anhydride was incorporated into the polymer to react with some of the attached acetamido groups; these would give imide crosslinks. A series of resins and glass-reinforced laminates incorporating these resins was prepared. The laminates were aged and tested at 315°C. Flexural strength at 315°C. versus hours aged at 315°C. is presented. Flexural strength after 100 hr. at 315°C. for two of the better laminates from modified polymers was about 48,000 psi, compared to 24,000 psi for the straight linear polymer. The flexural strength of the modified polymers decreased more rapidly, however, and after 1000 hr. of aging at 315°C. the flexural strength of the best laminates, including the linear polymer, was 12,000 psi.     

Metal-free dihydroxylation of alkenes using cyclobutane malonoyl peroxide

Cyclobutane malonoyl peroxide (7), prepared in a single step from the commercially available diacid 6, is an effective reagent for the dihydroxylation of alkenes. Reaction of a chloroform solution of 7 with an alkene in the presence of 1 equiv of water at 40 °C followed by alkaline hydrolysis leads to the corresponding diol (30-84%). With 1,2-disubstituted alkenes, the reaction proceeds with syn-selectivity (3:1 → 50:1). A mechanism consistent with experimental findings is proposed, which is supported by deuterium and oxygen labeling studies and explains the stereoselectivity observed. Alternative reaction pathways that are dependent on the structure of the starting alkene are also described leading to the synthesis of allylic alcohols and γ-lactones.     

Polybenzimidazoquinazolines: High-Temperature Matrix Materials

A series of polybenzimidazoquinazolines (PIQ) were prepared by the condensation of 5, 5′-bis[2(o-aminophenyl)benzimidazole] with phenyl esters of various di- and tricarboxylic acids. Thermomechanical and thermooxidative properties of the neat resins and as matrices in reinforced composites were evaluated at 371°C. A benzimidazoquinazoline copolymer, prepared from diphenyl bisbenzoate and sym-tris(carbophenoxyphenyl) triazine showed excellent retention of thermooxidative and thermomechanical properties at 371°C after 200 hr at 371°C. For example, a Modmor II unidirectional laminate provided flexural strength and modulus at 371°C, respectively, of 112, 000 psi and 15.6 × 10⁶ psi after 1 hr and 108, 000 and 16.4 × 10⁶ psi after 200 hr in circulating air.     

Comparison of microwave digestion procedures for the determination of some elements in asphaltite ash using ICP-AES

A microwave digestion procedure for asphaltite ash was developed in an attempt to facilitate routine analysis and obtain reproducible conditions or comparable results. The conditions of the most effective procedure for 0.1 g asphaltite ash samples are 1 ml of HNO3 + 3 ml of HCl + 1 ml of HF + 1 ml of deionized water as acid mixture and 15 min for digestion time. The digestion was accomplished in five stages applying continuously 90% to 20% of the microwave power and 20 to 100 psi of the pressure for 10 min of total time. Concentrations of selected elements, Cr, Co, Fe, Mn, Ni and Zn were measured using inductively coupled plasma-atomic emission spectroscopy. The proposed method of digestion provided precise results with relative standard deviations generally less than 3% for investigated elements. Results for fly ash as standard reference material was in good agreement with certified values.     

Grubbs' catalyst in paraffin: an air-stable preparation for alkene metathesis

A homogeneous mixture of Grubbs' catalyst in paraffin wax was shown to catalyze three important types of metathesis reactions: ring-closing metathesis, alkene dimerization, and alkene cross-metathesis (e.g., 11 --> 13). This catalyst preparation demonstrated no loss in catalytic activity after 22 months of storage open to the air.     

Poly(enonsulfides) from the addition of aromatic dithiols to aromatic dipropynones

Novel poly(enonsulfides) were prepared with inherent viscosities as high as 1.35 dL/g by nucleophilic addition of various aromatic dithiols to 1,1′-(1,3- or 1,4-phenylene)bis(3-phenyl-2-propyn-1-one) in m-cresol at 25–40°C. A tough clear yellow film with a tensile strength of 11,300 psi and a tensile modulus of 466,000 psi at 25°C was cast from a chloroform solution of the polymer prepared from 1,3-dithiobenzene and 1,1′-(1,4-phenylene)bis(3-phenyl-2-propyn-1-one). The poly(enonsulfides) exhibited T_g's as high as 180°C and weight losses of approximately 10% at 331°C in air. The synthesis and characterization of several poly(enonsulfides) are discussed.     

Preparation of nonsymmetrically substituted stilbenes in a one-pot two-step heck strategy using ethene as a reagent

We present here a strategy for the preparation of nonsymmetrically substituted stilbenes using a one-pot two-step double Heck strategy. First a protocol is developed for the selective preparation of a range of styrenes using ethene as the alkene coupling partner. Then conditions are found for the effective coupling of the styrenes with aryl halides using a 1:1 stoichiometric ratio of the two components. The use of the microwave apparatus to perform the reactions offers a convenient method for synthesis as well as for safely, easily, and accurately loading vessels with gaseous reagents.     

Evaluation of ferryl formation by electrocatalytic oxidation of alkene using luminol chemiluminescence

Electrochemical formation of ferryl porphyrin was examined by electrocatalytic oxidation of alkene by measuring luminol chemiluminescence using a flow-injection method. Emission was observed both below the reduction potential of Fe(III)TMPyP (-0.08 V at pH 11, -0.02 V at pH 7 and 0.15 V at pH 3) and above the oxidation potential (0.6 V at pH 11, 0.75 V at pH 7 and 1.1 V at pH 3). However, both anodic and cathodic emissions were inhibited significantly by the addition of alkene (cyclopent-2-ene-1-acetic acid) solutions downstream of the working electrode. Further, the spectra at both anodic and cathodic sides shifted to the longer wavelength (>424 nm) compared to the original spectrum of Fe(III)TMPyP (422 nm), which was not observed with the addition of alkene solution. Therefore, the results suggest that the electrochemically generated oxo-ferryl species have been engaged in catalytic oxidation of alkene before the flow reaches the observation cell.