A simple route to N-acylaminophosphonoacetates (N-protected phosphonylglycine esters).

Rhodium(II) acetate catalyzed reaction of tri-Et diazophosphonoacetate with amides, carbamates or ureas gives a range of N-acyl phosphonylglycine derivs. by N-H insertion reaction of the intermediate rhodium carbenoid.

Study of the transamidative ring expansion of N--halogenoalkyl--lactams of alkyl chain lengths 2–12 in liquid ammonia and other liquid amines: syntheses of 7-, 8- and 9-membered 1,5-diaza cyclic ketones, including routes to (±)-dihydroperiphylline and (±)-celabenzine

N-(3-Halogenopropyl)-4-phenylazetidin-2-ones undergo amination in liquid ammonia followed by transamidative ring expansion to give the eight-membered 4-phenyl -1,5-diazacyclooctan-2-one in excellent yield. Ring expansion of the amines in liquid ammonia is found to be much more effective than in hydrocarbon solvents. Formation of 7-, 8-, and 9-membered azalactams from the requisite -halogenoalkyl--lactams is an excellent synthetic process, though it is not applicable to 10membered rings. In the cases of rings of 13-, 15- and 17-members, although amination and apparent expansion takes place, the large rings appear not to be stable to ammonia and the final products are acyclic amides. N-[4-Halogenobut-2(Z)-enyl]-4-phenylazetidin-2-one satisfactorily forms a 9-membered (Z)-olefinic azalactam, but the (E)-isomer gives an acyclic amino amide. By using alkyl-substituted -lactam side-chains, C-substituted medium rings can be obtained; the relative instability of N-acyl -lactams to ammonia, however, leads to acylamino amides rather than expanded rings.Employing ethylamine in place of ammonia, it is shown that N-ethylated azalactams are formed satisfactorily, and using allylamine, N-allyl medium rings capable of further elaboration are obtained. The chemistry of these systems is discussed. Using transamidation in liquid ammonia, a short synthesis of the 9-membered spermidine alkaloid (±)-dihydroperiphylline is reported. Synthesis of key intermediates, whose transformation into the 13-membered alkaloids of the celabenzine group has already been effected, has been carried out.X-Ray single-crystal structure determinations for 4-phenyl-1,5-diazacyclononan-2-one, trans-4-phenyl-8-methyl-1,5-diazacyclooctan-2-one and (Z)-4-phenyl-1,5-diazacyclonon-7-en-2-one are reported, and comment is made on certain conformational features.

Thermochemistry of Ionic Liquid-Catalyzed Reactions: Theoretical and Experimental Study of the Beckmann Rearrangement-Kinetic or Thermodynamic Control?

A thermodynamic analysis of the experimental conditions of the Beckmann rearrangement reaction of oximes into amides has been undertaken to examine whether the reaction is under thermodynamic or kinetic control. To answer this question, the thermodynamic properties of the typical Beckmann rearrangement reactions in the ideal gaseous state-cyclohexanone oxime to caprolactam and 2-butanone oxime to N-methylpropanarnide-were studied by using the quantum mechanical method. Gibbs energy and equilibrium constants of the Beckmann rearrangement have been assessed in the gaseous and the liquid phases. Results of the thermodynamic analysis have shown that Beckmann rearrange ments are kinetically controlled. Thus, a search for possible active ionic liquid based catalysts for the mild reaction conditions has been performed.

Synthesis of nucleoside analogues in a ball mill: fast, chemoselective and high yielding acylation without undesirable solvents

The chemoselective acylation of primary aliphatic amines has been achieved in under ten minutes (and for aromatic amines under 120 min) using vibration ball-milling, avoiding undesirable solvents which are typically employed for such reactions (e.g. DMF). Under optimised conditions, the synthesis of amides in the presence of both primary and secondary alcohol functions was achieved in high to excellent yields (65-94%). Overall, the methods described have significant practical advantages over conventional approaches based upon bulk solvents including greater yields, higher chemoselectivity and easier product separation.

Evaluation of Pt and Re oxidation state in a pressurized reactor: difference in reduction between gas and liquid phase

Determination of metal oxidation state under relevant working conditions is crucial to understand catalytic behaviour. The reduction behaviour of Pt and Re was evaluated simultaneously as a function of support and solvent in a pressurized reactor (autoclave). The bimetallic catalysts are used in selective hydrogenation of carboxylic acids and amides. Gas phase reduction reduced the metals more efficiently, in particular Pt.

Binding site of AMPA-receptor allosteric modulator

The computer molecular docking of piperonyl acid piperidide (BDP) and some its analogs already known as ampakins was conducted for estimating their possible binding with AMPA-receptor glutamate domains in cyclothiazide binding area and for further design of new structures maximally complimentary to the receptor. On the base of the conducted docking it can be suggested that the binding site of BDP (amides of benzodioxane-6-carboxylic and piperonyl acids) analogs is located in AMPA-receptor cyclothiazide binding pocket. It is shown that formation of protein-ligand complexes of AMPA-receptor with benzodioxane-6-carboxylic and piperonyl acid derivatives, similarly to cyclothiazide, proceeds with interaction with Ser497, Leu751, which significance is confirmed by site-specific mutagenesis.

Novel ruthenium-terpyridyl complex for direct oxidation of amines to nitriles

High catalytic activity and selectivity has been demonstrated for the oxidation of both aliphatic and aromatic amines to nitriles under benign conditions with dioxygen or air using the Ru2Cl4(az-tpy)(2) complex. The conversion was found to be strongly influenced by the alkyl chain length of the reactant with shorter chain amines found to have lower conversions than those with longer chains. Importantly, by using the ruthenium terpyridine complex functionalized with azulenyl moiety at the 4 position of central pyridine core provided a much higher reactivity catalyst compared with a series of ruthenium terpyridine-based ligand complexes reported. Mechanistic studies using deuterated benzylamine demonstrated the importance of RuOH in this reaction.

Exploring molecular recognition pathways in one- and two-component gels formed by dendritic lysine-based gelators

This paper provides an integrated overview of the factors which control gelation in a family of dendritic gelators based on lysine building blocks. In particular, we establish that higher generation systems are more effective gelators, amide linkages in the dendron are better than carbamates, and long alkyl chain surface groups and a carboxylic acid at the focal point enhance gelation. The gels are best formed in relatively low polarity solvents with no hydrogen bond donor ability and limited hydrogen bond acceptor capacity. The dendrons with acid groups at the focal point can form two component gels with diaminododecane, and in this case, it is the lower generation dendrons which can avoid steric hindrance and form more effective gels. The stereochemistry of lysine is crucial in self-assembly, with opposite enantiomers disrupting each other's molecular recognition pathways. For the two-component system, stoichiometry is key, if too much diamine is present, dendron-stabilised microcrystals of the diamine begin to form. Interestingly, gelation still occurs in this case, and the systems with amides/alkyl chains are more effective gels, as a consequence of enhanced dendron-dendron intermolecular interactions allowing the microcrystals to form an interconnected network.

Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions

Ischaemic strokes evoke blood-brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho-kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho-kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil- versus vehicle-treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post-ischaemia or 4 h post-ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress- and tight junction-related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen-glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin-5. Cotreatment of cells with Y-27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho-kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions. Inhibition of Rho-kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle-treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y-27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition-mediated BBB protection.

Liquid coordination complexes: a new class of Lewis acids as safer alternatives to BF3 in synthesis of polyalphaolefins

Liquid coordination complexes (LCCs) are a new class of liquid Lewis acids, prepared by combining an excess of a metal halide (e.g. GaCl3) with a basic donor molecule (e.g. amides, amines or phosphines). LCCs were used to catalyse oligomerisation of 1-decene to polyalphaolefins (PAOs). Molecular weight distribution and physical properties of the produced oils were compliant with those required for low viscosity synthetic (Group IV) lubricant base oils. Kinematic viscosities at 100 °C of ca. 4 or 6 cSt were obtained, along with viscosity indexes above 120 and pour points below −57 °C. In industry, to achieve similar properties, BF3 gas is used as a catalyst. LCCs are proposed as a safer and economically attractive alternative to BF3 gas for the production of polyalphaolefins.

Magnitude differences in bioactive compounds, chemical functional groups, fatty acid profiles, nutrient degradation and digestion, molecular structure and metabolic characteristics of protein in newly developed yellow-seeded and black-seeded canola lines.

Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl, 3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 μmol/g) between the CS-Y and CS-B lines. For bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in protein structure makeup and conformation between the two lines. In terms of energy values, there were significant differences in total digestible nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM), and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B lines. For in situ rumen degradation kinetics, the two lines differed in soluble fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590 g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but no difference in degradation rate. CS-Y had higher digestibility of rumen bypass protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171 g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower in the CS-Y line, but there were no differences in total truly digested protein in small intestine (DVE) and feed milk value (FMV) between the two lines. In conclusion, the new yellow line had different nutritional, chemical, and structural features compared to the black line. CS-Y provided better nutrient utilization and availability.

A further investigation of the cytochrome b5–cytochrome c complex

J Biol Inorg Chem (2003) 8: 777–786

Effects of Local Anesthetic on the Time Between Analgesic Boluses and the Duration of Labor in Patient-Controlled Epidural Analgesia: Prospective Study of Two Ultra-Low Dose Regimens of Ropivacaine and Sufentanil

BACKGROUND: Patient-controlled epidural analgesia with low concentrations of anesthetics is effective in reducing labor pain. The aim of this study was to assess and compare two ultra-low dose regimens of ropivacaine and sufentanil (0.1% ropivacaine plus 0.5 μg.ml-1 sufentanil vs. 0.06% ropivacaine plus 0.5 μg.ml-1 sufentanil) on the intervals between boluses and the duration of labor. MATERIAL AND METHODS: In this non-randomized prospective study, conducted between January and July 2010, two groups of parturients received patient-controlled epidural analgesia: Group I (n = 58; 1 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil) and Group II (n = 57; 0.6 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil). Rescue doses of ropivacaine at the concentration of the assigned group without sufentanil were administered as necessary. Pain, local anesthetic requirements, neuraxial blockade characteristics, labor and neonatal outcomes, and maternal satisfaction were recorded. RESULTS: The ropivacaine dose was greater in Group I (9.5 [7.7-12.7] mg.h-1 vs. 6.1 [5.1-9.8 mg.h-1], p < 0.001). A time increase between each bolus was observed in Group I (beta = 32.61 min, 95% CI [25.39; 39.82], p < 0.001), whereas a time decrease was observed in Group II (beta = -1.40 min, 95% CI [-2.44; -0.36], p = 0.009). The duration of the second stage of labor in Group I was significantly longer than that in Group II (78 min vs. 65 min, p < 0.001). CONCLUSIONS: Parturients receiving 0.06% ropivacaine exhibited less evidence of cumulative effects and exhibited faster second stage progression than those who received 0.1% ropivacaine.

Reactions of some non-enolisable chloroketones with amide ion and a new synthesis of acridones /|nGuo-shyoung John Chen. -- 260 St. Catharines, Ont. : [s. n.],

This research was directed mainly towards the investigation of the reacti.ons of· substituted chlorobenziophenones under strongly basi,c conditions. The work 'can be divided into two main sections. The Introduction deals mainly with historical studies on aryne chemistry and the Haller-Bauer reaction. Secti.on I i.s concerned with syntheses of 2-benzamido-2'chlorobenzophenone and 2-benzamido~3'-chlorobenzophenone,and with thei,r respective reactions wi.th potassium amide in ammonia. o-Chlorophenylacetic acid was converted to the acid chloride and then by Friedel-Craftsreaction with benzene to w-(o-chlorophenyl)acetophenone. Reaction wi.th phenylhydrazine and Fischer cyclization gave 3- (0chlorophenyl)- 2-phenylindole, which was ozonized to 2-benzamido-2'chlorobenzophenone. The isomeric 3' -chlor,..o ke: tone was similarly synthesised from m-chlorophenylacetic acid. Both the 2'- and 3' -ch.loroketones gave N-benzoylacridone on treatment with potassium amide in ammonia; an aryne mechanism is involved for the 3'-chloroketone but aryne and nucleophilic substitution mechanisms are possible for the 2'-chloroketone. Hydrolysis of the 2'- and 3'-chloroketones gave 2-amino-2'chlorobenzophenone and 2-amino-3'-chlorobenzophenone respectively. A second new acridone synthesis is given in the Appendix involving reactions of these two ketones with potassium t-butoxide in t-butylbenzene. i Section 2 deals with the investigation of the reaction of some tricyclic ch1orobenzophenones with potassium amide in liquid ammonia. These were 1-ch1orof1uorenone; which was pr~pared in several steps from f1uoranthene, and 1- and 2-ch1oroanthraquinones. 1-Ch1orof1uorenone gave 1-aminof1uorenone ; 1-ch1oroanthraquinone gave 1- and 2-aminoanthraquinones; 2-ch1oroanthraquinone was largely recovered from the attempted reaction.

ORGANOSILICON BIOTECHNOLOGY: A BIO-INSPIRED APPROACH TO THE HYDROLYSIS OF ALKOXYSILANES and THE LIPASE-CATALYZED SYNTHESIS OF SILOXANE-CONTAINING POLYESTERS AND POLYAMIDES

The first part of this thesis studied the capacity of amino acids and enzymes to catalyze the hydrolysis and condensation of tetraethoxysilane and phenyltrimethoxysilane. Selected amino acids were shown to accelerate the hydrolysis and condensation of tetraethoxysilane under ambient temperature, pressure and at neutral pH (pH 7±0.02). The nature of the side chain of the amino acid was important in promoting hydrolysis and condensation. Several proteases were shown to have a capacity to hydrolyze tri- and tet-ra- alkoxysilanes under the same mild reaction conditions. The second part of this thesis employed an immobilized Candida antarctica lipase B (Novozym-435, N435) to produce siloxane-containing polyesters, polyamides, and polyester amides under solvent-free conditions. Enzymatic activity was shown to be temperature dependent, increasing until enzyme denaturation became the dominant pro-cess, which typically occurred between 120-130ᵒC. The residual activity of N435 was, on average, greater than 90%, when used in the synthesis of disiloxane-containing polyesters, regardless of the polymerization temperature except at the very highest temperatures, 140-150ᵒC. A study of the thermal tolerance of N435 determined that, over ten reaction cycles, there was a decrease in the initial rate of polymerization with each consecutive use of the catalyst. No change in the degree of monomer conversion after a 24 hour reaction cycle was found.