Bifunctional Amino Research Articles

Highly Diastereo- and Enantioselective Organocatalytic Michael Addition of α-Ketoamides to Nitroalkenes

The first organocatalytic enantio- and diastereoselective conjugate addition of α-ketoamides to nitroalkenes has been achieved using a bifunctional amino thiourea catalyst. In this new approach, the substrate amide proton plays a critical role in the formation of the Michael anti-adducts in high yields and high stereoselectivities. To illustrate the high synthetic potential of this methodology, the diastereo- and enantioselective synthesis of a hexasubstituted cyclohexane via a Michael-Michael-Henry cascade reaction is described.

ChemInform Abstract: Synthesis of an Orthogonally-Protected Bifunctional Amino Acid for Conformationally Constrained Peptides.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of functional poly(phenyl isocyanide)s with macromolecular helicity memory and their use as asymmetric organocatalysts

To develop a novel polymer-based asymmetric organocatalyst, a series of helical poly(phenyl isocyanide)s with functional pendant groups were prepared by modifying the side groups of the optically active helical poly(4-carboxyphenyl isocyanide) with a macromolecular helicity memory. Helical polyisocyanides partially modified with achiral amines, such as piperazine, maintained their chiral memory and enantioselectively catalyzed a direct aldol reaction. Although the enantioselectivity was low, the original helical poly(4-carboxyphenyl isocyanide) showed no catalytic activity. These results indicated that the macromolecular helicity of the modified polyisocyanides together with bifunctional amino and carboxy acid pendant residues arranged in a helical array along the polymer backbones plays an important role in the enantioselectivity.

Direct Asymmetric Iodination of Aldehydes Using an Axially Chiral Bifunctional Amino Alcohol Catalyst

A direct asymmetric iodination reaction of aldehydes with NIS was found to be catalyzed by the novel axially chiral bifunctional amino alcohol (S)-1d. This method represents the rare example of the catalytic and highly enantioselective synthesis of optically active alpha-iodoaldehydes.

The Amino Thiourea-Catalyzed Asymmetric Nucleophilic Reactions

Bifunctional amino thiourea-catalyzed asymmetric additions of several nucleophiles into electron-deficient unsaturated compounds such as nitroolefins, ?,?-unsaturated imides, imines, and azodicarboxylates are described. We discovered that bifunctional thioureas bearing a tertiary amino group significantly accelerated several nucleophilic addition reactions of active methylene compounds to electron-deficient double bonds. In these reactions, a strong hydrogen-bonding ability of the thiourea moiety as well as an appropriate Brønsted basicity of the tertiary amine is crucial for high enantioselectivity. This dual activation of both nucleophiles and electrophiles by the bifunctional thiourea expanded the applicability of the thiourea-catalyzed enantioselective reaction. In addition, these organocatalyzed asymmetric reactions were successfully applied to the concise asymmetric synthesis of natural products and medicinal candidates such as epibatidine, baclofen, and CP-99,994.

A new bifunctional amino acid chelator targeting the glucose transporter

The coupling reactions of d-glucosamine, 1,3,4,6-tetra- O-acetylglucosamine, and 4-aminophenyl-galactopyranosine with N, N-bis(quinolinoyl)aminovaleric acid ( L1) provided a series of conjugates containing a potentially tridentate donor group terminus linked to a sugar moiety, L2′, L2 and L3, respectively. Reactions of the ligands with [NEt 4] 2[Re(CO) 3Br 3] in refluxing methanol provided the rhenium complexes [Re(CO 3)( L1)]Br ( ReL1), [Re(CO) 3( L2)]Br ( ReL2), [Re(CO) 3( L2′)]Br ( ReL2′) and [Re(CO) 3( L3)]Br ( ReL3). The ligands and complexes were characterized by elemental analyses, 1H and 13C NMR, mass spectroscopy and, in the case of L1 and ReL1, by X-ray crystallography. The rhenium complexes exhibit fluorescence emissions with long lifetimes, large Stokes shifts, and moderate quantum yields.

Mechanism and Scope of Salen Bifunctional Catalysts in Asymmetric Aldehyde and α‐Ketoester Alkylation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mechanism and scope of salen bifunctional catalysts in asymmetric aldehyde and α-ketoester alkylation

Metal complexes of C 2-symmetric Lewis acid/Lewis base salen ligands provide bifunctional activation resulting in rapid rates in the enantioselective addition of diethylzinc to aldehydes (up to 92% ee). Further experiments probed the reactivity of the individual Lewis acid and Lewis base components of the catalyst and established that both moieties are essential for asymmetric catalysis. These catalysts are also effective in the asymmetric addition of diethylzinc to α-ketoesters. This finding is significant because α-ketoesters alone serve as their own ligands to accelerate racemic 1,2-carbonyl addition of Et 2Zn and racemic carbonyl reduction. The latter proceeds via a metalloene pathway, and often accounts for the predominant product. Singular Lewis acid catalysts do not accelerate enantioselective 1,2-addition over these two competing paths. The bifunctional amino salen catalysts, however, rapidly provide enantioenriched 1,2-addition products in excellent yield, complete chemoselectivity, and good enantioselectivity (up to 88% ee). A library of the bifunctional amino salens was synthesized and evaluated in this reaction. The utility of the α-ketoester method has been demonstrated in the synthesis of an opiate antagonist.

ChemInform Abstract: Design and Synthesis of Bifunctional Amino Phosphonic Haptens for Catalytic Antibody Production.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Design and Synthesis of Bifunctional Amino Phosphonic Haptens for Catalytic Antibody Production

Bifunctional amino phosphonic haptens were designed to mimic Soman structurally and were synthesized and conjugated to carrier proteins for the generation of monoclonal antibodies.

Synthesis of an Orthogonally-Protected Bifunctional Amino Acid for Conformationally Constrained Peptides

The asymmetric synthesis of ( 2S, 9R)-2,9-diaminodecanedioic acid, orthogonally protected for incorporation into cyclic peptides by solid-phase synthesis, is described. © 1997 Published by Elsevier Science Ltd.

Investigation into the membrane alteration relevant to the mechanism of thermohaemolysis

The mechanism of thermohaemolysis above 48°C was recently revealed as being of colloid-osmotic type. The permeability barrier damage responsible is insensitive to the displacement of cytosol by isotonic NaCl/sucrose media and is related to a thermally induced event in the erythrocyte membrane (EM) at 62°C, which presumably involves heat alteration of membrane proteins, excluding spectrin and the anion channel. The onset temperature of this event is linearly reduced by ethanol in intact cells and resealed ghosts with sensitivity exceeding 3.5 times that of heat denaturation of spectrin. Thus, at a specific concentration of ethanol (18% v/v), the permeability breakdown event occurs at 39°C, which precedes the spectrin denaturation by 6°C, a result which was used here independently to induce and study this event. The event was induced by heating intact cells or resealed ghosts for 3 min in the presence of 18% ethanol at 39.5°C. Using thermal gel analysis it was established that this event was not accompanied by an intermolecular disulfide bond aggregation of membrane proteins, a phenomenon which usually follows the heat denaturation of proteins. The membranes of cells and ghosts, exposed to different temperatures for 3 min in the presence of 18% (v/v) ethanol, were subjected to SDS-PAGE after modification with the bifunctional amino reagent FNPS (4,4′-difluoro-3,3′-dinitrodiphenylsulfone). The electrophoretic profile obtained strongly depended on the temperature of exposure. If the latter was between 20 and 35°C, the gel pattern did not differ from that of the intact EM, but if this temperature coincided with the onset temperature (39°C), the gel profile indicated the occurrence of strong cross-linkage of membrane proteins. These results showed that the 62°C membrane event involved only a limited conformational change in EM proteins, possibly in some intrinsic ones, during which many reactive groups appeared at a distance, allowing cross-linking by a bifunctional agent but not a direct aggregation of the altered proteins.

Free energies of adsorption of amino acids, short linear peptides and 2,5-piperazinediones on silica from water as estimated from high-performance liquid-chromatographic retention data

Equilibrium constants (K) and free energies (— ΔG) of adsorption of amino acids, short linear peptides and cyclic dipeptides (2,5-piperazinediones) on silica from neutral aqueous solutions were calculated from the retention values measured by means of high-performance liquid chromatography on a silica gel column. For most amino acids and linear peptides — ΔG values were negative and K 0 and K > 1) as compared to related dipeptides. Influence of the structure of a-substituent on the adsorbability is analyzed. A linear dependence of — ΔG on the number of aliphatic carbon atoms in a sorbate molecule was found for the series of aliphatic bifunctional amino acids, related dipeptides and 2,5-piperazinediones, as well as for the group from glycine to triglycyl glycine.

Adsorption of small biological molecules on silica from diluted aqueous solutions: Quantitative characterization and implications to the Bernal's hypothesis

To describe quantitatively the adsorption of prebiotically important compounds of low molecular weight (amino acids, short linear peptides, cyclic dipeptides, the Krebs's cycle and other carboxylic acids, nucleosides and related phosphates) on silica surface from diluted neutral aqueous solutions, equilibrium constants (K) and free energies (-delta G) of adsorption were determined from the retention values measured by means of high-performance liquid chromatography on a silica gel column and from the isotherms measured under static conditions. For most carboxylic acids (including amino acids and linear peptides) -delta G values were negative and K < 1, thus showing very weak adsorption. Cyclic dipeptides (2,5-piperazinediones) exhibited higher adsorbability; -delta G > 0 and K > 1 were found for most of them. Influence of the structure of alpha-substituent on the adsorbability is analyzed. A linear dependence of -delta G on the number of aliphatic carbon atoms in a sorbate molecule was found for the series of aliphatic bifunctional amino acids, related dipeptides and 2,5-piperazinediones, as well as for the row from glycine to triglycyl glycine. The adsorption of nucleosides and their phosphates is characterized by much higher K and -delta G values (of the order of 10(2) and 10(4), respectively). The adsorption data available from our work and literature are summarized and discussed with implications to the Bernal's hypothesis on the roles of solid surfaces in the prebiotic formation of biopolymers from monomeric 'building blocks'.

Multilayer Enzyme Assembly for the Development of a Novel Fiber Optic Biosensor

AbstractWe have developed a technique to immobilize a multilayer enzyme assembly on an optical fiber surface. The technique utilizes a bifunctional amino coupling agent to link between different layers of enzymes. The method offers the flexibility of controlling the number of enzymes on a fiber surface. Multilayers of enzyme — Alkaline Phosphatase have been characterized using ellipsometry and surface plasma resonance. Chemiluminecence experiments have been conducted as a function of number of enzyme layers. The results indicated that at least 3 layers of enzyme can be assembled on a fiber surface. Utilising the new immobilization technique, a novel fiber optic biosensor system for the detection of organophosphorous-based pesticide has been developed. The detection mechanism is the pesticide inhibition of alkaline phosphatase catalyzed chemiluminescence. As a model analyte, paraoxon with ppb level concentration has been detected.

Free Energies of Adsorption of Dipeptides and 2,5-Piperazinediones on Silica from Neutral Aqueous Solutions as Estimated from High-Performance Liquid-Chromatographic Retention Data

The equilibrium constants (K) and free energies (-∆G) of adsorption of dipeptides and their cyclic derivatives, 2,5-piperazinediones, on silica from neutral aqueous solutions were calculated from their HPLC retention data on a silica gel column. For the majority of the dipeptides -∆G values were negative, ranging from -1 170 to 430 J mol-1, and K &lt; 1, thus indicating a very weak adsorption. The 2,5-piperazinediones under study exhibited higher adsorbabilities (-∆G -1 070 + 3 030 J mol-1, K &gt; 1) as compared to the respective dipeptides. The effect of the α-substituent structure on the adsorbability is analyzed. A linear dependence of -∆G on the number of aliphatic carbon atoms in a sorbate molecule was observed for the series of dipeptides and 2,5-piperazinediones derived from bifunctional aliphatic amino acids.

Chemical transformations of proteinogenic amino acids during their sublimation in the presence of silica

Proteinogenic amino acids were sublimed in gram quantities in the presence of silica. High-performance liquid chromatographic and fast-atom-bombardment mass-spectrometric measurements showed that diketopiperazines (DKPs) were the main products of silica catalyzed thermal transformations in the case of aliphatic bifunctional amino acids. Intensive formation of products of decarboxylation, deamination and some other reactions was observed in the cases of trifunctional amino acids and phenylalanine. Possible mechanisms of reactions occured have been discussed. Principal possibility of ‘gas-solid-phase’ DKP synthesis has been demonstrated for bifunctional aliphatic amino acids.

Mechanisms of amino acid polycondensation on silica and alumina surfaces

Chemisorption products of bifunctional amino acid vapours on the surface of silica and alumina have been studied by the method of infrared spectroscopy. On the basis of the analysis of spectral data it is supposed that heterogeneous polycondensation of amino acids with formation of peptides proceeds under these conditions. The supposition was confirmed by the study of products of interaction of amino acid vapours with silica and alumina by the method of fast atom bombardment mass-spectrometry. It is established that in contrast to alumina the condensation of amino acids into linear peptides on silica surface proceeds only at presence of at least small amounts of water. The most probable mechanisms of extending of peptide chains are proposed on the basis of obtained experimental data.

Dissociation, cross-linking, and glycosylation of the coated vesicle proton pump.

In order to refine further our structural model of the coated vesicle (H+)-ATPase (Arai, H., Terres, G., Pink, S., and Forgac, M. (1988) J. Biol. Chem. 263, 8796-8802), we have extended our structural analysis to identify peripheral and glycosylated subunits of the pump as well as to identify subunits which are in close proximity in the native (H+)-ATPase complex. Treatment of the purified, reconstituted (H+)-ATPase with 0.30 M KI in the presence or absence of ATP or MgATP results in the release of the 73-, 58-, 40-, 34-, and 33-kDa subunits, leaving behind the 100-, 38-, 19-, and 17-kDa subunits in the membrane. Because the former group of polypeptides is released from the membrane in the absence of detergent, they correspond to peripheral membrane proteins. To determine which subunits are in close proximity, cross-linking of the purified (H+)-ATPase was carried out using the cleavable, bifunctional amino reagent 3,3'-dithiobis(sulfosuccinimidylpropionate) followed by two-dimensional gel electrophoresis. These studies indicate that contact regions exist between the 73- and 58-kDa subunits as well as between the 17-kDa subunit and the 40-, 34-, and 33-kDa subunits. To test for glycosylation of the (H+)-ATPase, the detergent-solubilized complex was treated with neuraminidase followed by electrophoresis and blotting using a peanut lectin/horseradish peroxidase conjugate. Galactose-inhibitable staining of the 100-kDa subunit, together with affinity chromatography of the intact (H+)-ATPase on peanut lectin agarose, indicates that the 100-kDa subunit is glycosylated, most likely at a site exposed on the luminal side of the membrane. These results, together with those presented in the preceding paper (Adachi, I., Arai, H., Pimental, R., and Forgac, M. (1990) J. Biol. Chem. 265, 960-966), were used in the construction of a refined model of the coated vesicle (H+)-ATPase.

IR spectra of bifunctional ?-amino acids sorbed on dehydrated aerosil

IR spectroscopy has been applied to sorption products from the vapors of bifunctional amino acids derived from proteins: glycine, alanine, valine, leucine, isoleucine, phenylalanine, and methionine, which have been used with dehydrated aerosil. Three types of sorption complexes are formed: two hydrogen-bonded ones and a covalent one, which is of ester or mixed anhydride type. The IR spectra and other tests suggest structures for the complexes and formation schemes.