4-pentynoic Acid Research Articles

Effective PHIP labeling of bioactive peptides boosts the intensity of the NMR signal.

A series of novel bioactive derivatives of the sunflower trypsin inhibitor-1 (SFTI-1) suitable for hyperpolarization by parahydrogen-induced polarization (PHIP) was developed. The PHIP activity was achieved by labeling with L-propargylglycine, O-propargyl-L-tyrosine, or 4-pentynoic acid. (1) H NMR signal enhancements (SE) of up to a factor of 70 were achieved in aqueous solution. We found that an isolated spatial location of the triple bond within the respective label and its accessibility for the hydrogenation catalyst are essential factors for the degree of signal enhancement.

Macromol. Rapid Commun. 2/2014

Front Cover: A possible strategy to encrypt information at the molecular level is the creation of a binary code using two co-monomers defined as 0 and 1. As a proof of principle, sequence-defined oligo(triazole amide)s are synthesized via a stepwise solid-phase iterative process. In this approach, a reactive spacer, namely 1-amino-11-azido-3,6,9-trioxaundecane, is reacted with either 4-pentynoic acid (non-coding monomer) or 2-methyl-4-pentynoic acid (coding monomer). All possible information triads, 000, 001, 010, 100, 011, 101, 110, and 111 can be obtained using this approach. Further details can be found in the article by T. T. Trinh, L. Oswald, D. Chan-Seng, and J.-F. Lutz* on page 141.

Thermoresponsive ureido-derivatized polymers: the effect of quaternization on UCST properties

A series of thermoresponsive ureido-derivatized polymers were synthesized via atom transfer radical polymerization (ATRP) and a post-modification process. All of the polymers were designed to exhibit an upper critical solution temperature (UCST) in aqueous solution, which was mainly dependent on (i) the presence of ureido moieties, (ii) the chain length of the side groups, and (iii) the degree of quaternization (DQ) on a triazole ring. Side group modification of PHEMA was carried out by DCC coupling with 4-pentynoic acid to prepare PHEMA-alkyne (PHA). 2-Azidoethylurea and 3-azidopropylurea were combined with the PHA backbone via click reaction, resulting in triazole-ring containing ureido-derivatized polymers. Quaternization reactions with methyl iodide were conducted on the triazole ring of each polymer to further control the UCSTs. Results showed that the UCST could be precisely tuned by the level of DQ.

Synthesis of Molecularly Encoded Oligomers Using a Chemoselective “AB + CD” Iterative Approach

A library of eight sequence-defined model oligomers, whose sequence is based on a (0,1) binary code, is prepared through chemoselective repeating cycles of amidification and copper-assisted alkyne-azide cycloaddition reactions from a non-modified Wang resin. This library is constructed from two AB (A = acid, B = alkyne) building blocks, i.e., 4-pentynoic acid and 2-methyl-4-pentynoic acid acting, respectively, as non-coding (0) and coding (1) monomer, and 1-amino-11-azido-3,6,9-trioxaundecane as complementary CD (C = amine, D = azide) spacer building block. In particular, encoded triads are synthesized by consecutive covalent attachment of five building blocks (i.e., three coding/non-coding monomers and two spacers). In this communication, optimal protocols for the synthesis of the targeted oligomers are reported along with their full characterization by (1) H NMR, MALDI-TOF mass spectrometry, and size-exclusion chromatography. It is found that all possible encoded triads (i.e., eight possibilities) could be synthesized using this approach. Indeed, monodisperse sequence-defined oligomers are prepared and characterized in all cases.

Versatile on-resin synthesis of high mannose glycosylated asparagine with functional handles

Here we present a synthetic route for solid phase synthesis of N-linked glycoconjugates containing high mannose oligosaccharides which allows the incorporation of useful functional handles on the N-terminus of asparagine. In this strategy, the C-terminus of an Fmoc protected aspartic acid residue is first attached to a solid phase support. The side chain of aspartic acid is protected by a 2-phenylisopropyl protecting group, which allows selective deprotection for the introduction of glycosylation. By using a convergent on-resin glycosylamine coupling strategy, an N-glycosidic linkage is successfully formed on the free side chain of the resin bound aspartic acid with a large high mannose oligosaccharide, Man8GlcNAc2, to yield N-linked high mannose glycosylated asparagine. The use of on-resin glycosylamine coupling provides excellent glycosylation yield, can be applied to couple other types of oligosaccharides, and also makes it possible to recover excess oligosaccharides conveniently after the on-resin coupling reaction. Useful functional handles including an alkene (p-vinylbenzoic acid), an alkyne (4-pentynoic acid), biotin, and 5-carboxyfluorescein are then conjugated onto the N-terminal amine of asparagine on-resin after the removal of the Fmoc protecting group. In this way, useful functional handles are introduced onto the glycosylated asparagine while maintaining the structural integrity of the reducing end of the oligosaccharide. The asparagine side chain also serves as a linker between the glycan and the functional group and preserves the native presentation of N-linked glycan which may aid in biochemical and structural studies. As an example of a biochemical study using functionalized high mannose glycosylated asparagine, a fluorescence polarization assay has been utilized to study the binding of the lectin Concanavalin A (ConA) using 5-carboxyfluorescein labeled high mannose glycosylated asparagine.

In situ assembly of porous Au-paper electrode and functionalization of magnetic silica nanoparticles with HRP via click chemistry for Microcystin-LR immunoassay

A simple, low-cost and sensitive origami electrochemical immunoassay-device was developed based on a novel gold nanoparticle modified porous paper working electrode (Au-PWE) for point-of-care testing. Azide-functionalized Au-PWE was prepared by the functionalization of Au-PWE with 1-azidoundecan-11-thiol. Alkyne end-terminated antibody was prepared with 4-pentynoic acid and antibody by the 1-ethyl-3-(3-(dimethylamino) propyl) carbodiimide hydrochloride and N-hydroxysuccinimide activation reaction. Alkyne-antibody was coupled to azido-Au-PWE by click reaction as a recognition element. Nearly monodispersed sphere-like silica-coated ferroferric oxide (Fe3O4@SiO2) nanoparticles were prepared via the reverse microemulsion method. Azide-functionalized Fe3O4@SiO2 was prepared by the functionalization of silica shell with 3-bromopropyltrichlorosilane followed by substitution with sodium azide. Alkyne-functionalized antibody and horse radish peroxidase were coupled to azide-functionalized Fe3O4@SiO2 by click reaction as signal label. Horse radish peroxidase and ferroferric oxide could catalyze the oxidation of thionine in the presence of hydrogen peroxide. After the sandwich immunoreaction, the current was proportional to the logarithm of the Microcystin-LR. The linear regression equation was i(μA)=119.89+46.27logcMC-LR (μg/mL) in the range from 0.01 to 200μg/mL. The limit of detection was 0.004μg/mL. This immunoassay would provide a universal immunoassay method in environmental monitoring and public health.

Synthesis and Characterization of Oxygen/Sulfur-Bridged Incomplete Cubane-Type Clusters, [M3S4(Tpe)3]+ and [M3OS3(Tpe)3]+ (M = Mo and W), and a Mixed-Metal Cubane-Type Cluster, [Mo3PdS4Cl(Tpe)3

Abstract The reaction of [Mo3S4(H2O)9]4+ (1) and [Mo3OS3(H2O)9]4+ (2) with hydrotris(pyrazolyl)ethanol (HTpe) ligands produced [Mo3S4(Tpe)3]PF6·3CH2Cl2 ([5]PF6·3CH2Cl2) and [Mo3OS3(Tpe)3]PF6·4CH2Cl2 ([6]PF6·4CH2Cl2), respectively, using solvent extraction. Furthermore, the tungsten analogous compounds, [W3S4(Tpe)3]PF6·4CH2Cl2 ([7]PF6·4CH2Cl2) and [W3OS3(Tpe)3]PF6·2.5CH2Cl2 ([8]PF6·2.5CH2Cl2) have been prepared using a similar procedure to that used in the preparation of 5. The cyclic voltammograms of 5, 6, and 7 show one reversible one-electron oxidation process and one reversible one-electron reduction process (5, E1/2 = −0.96 and 1.10 V; 6, E1/2 = −0.96 and 1.00 V; 7, E1/2 = −1.54 and 0.77 V: all values are given vs. SHE). Complex 8 also shows one reversible (E1/2 = 0.61 V) and one irreversible one-electron oxidation processes (Epc = 1.12 V) and one irreversible one-electron reduction process (Epc = −1.54 V). The reaction of 5 with organometallic compound [Pd2(dba)3] in CH3CN afforded [Mo3PdS4Cl(Tpe)3]·4.5CH2Cl2 ([11]·4.5CH2Cl2). Complex 11 showed a high catalytic activity for the intramolecular cyclization of 4-pentynoic acid to give γ-methylene-γ-butyrolactone in the presence of Et3N. X-ray structure analyses of [5]PF6·3CH2Cl2, [6]PF6·4CH2Cl2, [7]PF6·4CH2Cl2, [8]PF6·2.5CH2Cl2, and [11]·4.5CH2Cl2 revealed that each molybdenum or tungsten atom is bonded to the Tpe ligand.

Au(I)/Ag(I)-Catalyzed Cascade Approach for the Synthesis of Benzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazolinones

An efficient and facile Au(I)/Ag(I)-catalyzed cascade method has been developed for one-pot synthesis of the complex polycyclic heterocycles benzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazolinone derivatives through treatment of the substituted 2-(1H-benzo[d]imidazol-2-yl)anilines with 4-pentynoic acid or 5-hexynoic acid. The strategy features a Au(I)/Ag(I)-catalyzed one-pot cascade process involving the formation of three new C-N bonds in high yields, and with broad a substrate scope.

An effective method for the preparation of chlorolactones

Abstract The effective chlorolactonization of alkenoic acids with (diacetoxyiodo)benzene and lithium chloride under mild conditions have been studied. Experiments show that various 4-pentenoic acids react with (diacetoxyiodo)benzene and lithium chloride fluently in CH3OH at room temperature, obtaining five-membered chlorolactones in good yields in short times. Other alkenoic acids, such as 3-butenoic acid and trans 3-hexenoic acid give some more complicated results, and 4-pentynoic acid provides a chloroenol lactone with Z configuration in 40% of yield.

Vanadium bromoperoxidase from Delisea pulchra: enzyme-catalyzed formation of bromofuranone and attendant disruption of quorum sensing

Vanadium bromoperoxidase was isolated and cloned from the marine red alga Delisea pulchra. This enzyme catalyzes the bromolactonization of 4-pentynoic acid forming 5E-bromo-methylidenetetrahydro-2-furanone, a compound which is shown herein to inhibit quorum sensing in the engineered reporter strain, Agrobacterium tumefaciens NTL4.

Rhodium(i) complexes bearing N-donor ligands: catalytic activity towards intramolecular cyclization of alkynoic acids and ligand lability

The structures of rhodium(I) complexes bearing tris(pyrazol-1-yl)toluidine (tpt) and tris(N-methylimidazol-2-yl)methanol (tim) ligands were examined in the solid state using single crystal X-ray diffraction, and in the solution state using variable temperature NMR spectroscopy. The solid state structures of the rhodium(I) tpt and rhodium(I) tim complexes showed that the ligands are bound to the rhodium(I) centre in the κ2 binding mode, rather than the κ3 binding mode. In the solution state, rhodium(I) complexes bearing the tpt ligand undergo fluxional behaviour at room temperature, which was attributed to rotation of the toluidine substituent about the C–C bond or the equilibrium between κ2 and κ3 binding modes. At low temperatures, rhodium(I) complexes bearing the tpt ligand adopted the κ2 binding mode, consistent with the coordination mode in the solid state structures. The efficiency of the complexes as catalysts for the intramolecular hydroalkoxylation of 4-pentynoic acid and 5-hexaynoic acid to form the corresponding lactone was established. The presence of the third unbound N-donor was shown to reduce the catalytic efficiency of the complexes with tridentate ligands when compared to their counterparts bearing bidentate ligands, due to either the steric hindrance or competitive binding of the third N-donor with the substrate during the catalytic cycle.

ChemInform Abstract: 5-Vinyl-4-pentynoic Acids Through the Palladium-Catalyzed Reaction of 4-Pentynoic Acid with Vinyl Triflates.

ChemInform Abstract: 5-Vinyl-4-pentynoic Acids Through the Palladium-Catalyzed Reaction of 4-Pentynoic Acid with Vinyl Triflates.

Covalent immobilization of redox protein via click chemistry and carbodiimide reaction: Direct electron transfer and biocatalysis

In this paper, a simple, facile and general strategy was proposed for the covalent biofunctionalization of Au surface with hemoglobin (Hb). Structurally well-defined azide-terminated organic self-assembled monolayers (SAMs) were formed on Au surface from a mixture solution of azidoundecanethiol and dilute thiol. 4-Pentynoic acid was used as a bifunctional linker to immobilized Hb via a selective, reliable, robust click reaction and a widely used carbodiimide reaction. The surface modification was characterized by reflectance absorption infrared (RAIR) spectroscopy, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The experimental data indicate that the proposed methodology is a highly versatile strategy for quantitative, stable and covalent attachment of biomacromolecules onto solid interface. The Hb functionalized Au electrode shows a pair of well-defined and quasi-reversible peaks at about −0.210 V (vs. SCE) in 0.1 mol/L pH 5.0 buffers, which stands for the reduction and oxidation of Hb Fe(III)/Fe(II) redox couple. The electron transfer rate constant ( k s ) was estimated to be 0.78 s −1. The maximal surface coverage ( Г) of the immobilized Hb was 8.3 × 10 −12 mol cm −2, indicating the formation of a monolayer. Moreover, the biocatalytic activity of the Hb biofunctonalized electrode was investigated and an excellent electrocatalytic reduction toward O 2 and H 2O 2 was observed.

Investigation of lanthanide(III) coordination compounds with 4-pentynoic acid

Coordination compounds of a new type, Ln(C 5H 5O 2) 3⋅2H 2O (where Ln = Pr 3+, Nd 3+, Eu 3+; C 5 H 5 O 2 - = 4-pentynoic anion), have been obtained in solution and as crystals. Spectroscopic investigations of the title compounds at room and low temperatures were performed in order to understand the electrostatic nature of the Ln 3+ ligand bond. The influence of the C C triple connection in carboxylate ions on the distribution of charge, polarity, strength, and character of the Ln O(L) coordination bond is analysed. The variation of spectroscopic parameters (e.g. δ) and their correlation with the nature of the Ln 3+ L bond are discussed. Investigation of these properties is very important because of the application of lanthanide carboxylates as catalyst precursors.

Heterogeneous Catalysis of a Copper-Coated Atomic Force Microscopy Tip for Direct-Write Click Chemistry

We report a constructive scanning probe lithography method that uses heterogeneous copper-coated atomic force microscopy tips to catalyze azide-alkyne cycloadditions (CuAAC) between solvated terminal alkyne molecules and azide-terminated self-assembled monolayers on silicon surfaces. Spatially controlled surface functionalization was carried out successfully with 50 mM ethanolic solutions of small molecules bearing terminal alkyne groups--propargylamine, 4-pentynoic acid, and an alkynyl-oligoethyleneoxide. We observed that reaction occurs only where the copper tip is in contact with an azide-terminated surface resulting in features with linewidths on the order of 50 nm. The extent of surface functionalization, as measured by changes in surface topography and lateral force microscopy, depends on the scanning force (31-350 nN) and scanning speed, with significant surface patterning observed even at speeds as high as 64 microm/s. In contrast with related SPL techniques, this approach affords a direct-write lithographic approach to constructively modifying and patterning surfaces at the nanoscale without the need for auxiliary reagents. All that is required is (1) an azide surface, (2) a solution of a terminal alkyne, and (3) a copper-coated AFM tip. These advantages allow the direct attachment of a potentially limitless library of molecules that bear terminal alkyne functionalities, including biomolecules, under relatively mild conditions, with sub-100 nm spatial resolution.

Friedel–Crafts acylation of ferrocene with alkynoic acids

Abstract Ferrocene reacts with alkynoic acids (conjugated or nonconjugated terminal), trifluoroacetic anhydride and triflic acid (or boron trifluoride etherate) to afford the corresponding ferrocenyl ynones in good yields. Only in the case of propynoic- and 3-butynoic acid complex, untreatable reaction mixtures were obtained. However, propynoilferrocene was obtained by desilylation of (trimethylsilyl)propynoilferrocene with KF/18-crown-6. Reaction with nonconjugated terminal alkynoic acids, carried out in the presence of a large excess of triflic acid (4 equiv.) results in formation of complex mixtures of products (in the reaction with 4-pentynoic acid enol triflate of ferrocenyl 1,4-diketone and 2-ferrocenyl-5-methylfuran were isolated). Ferrocenyl ynones obtained in this work can be used for synthesis of more complex ferrocenyl systems by “click” chemistry.

Synthesis of adaptative and amphiphilic polymer model conetworks by versatile combination of ATRP, ROP, and “Click chemistry”

Well-defined adaptative and amphiphilic polymer conetworks based on hydrophilic poly(N,N-dimethylamino-2-ethyl methacrylate) (PDMAEMA) and hydrophobic poly(e-caprolactone) (PCL) have been prepared by combination of ATRP, ROP, and Click chemistry. Telechelic α,ω-alkyne terminated PCL crosslinker was obtained by ring-opening polymerization (ROP) of CL in THF at 80 °C initiated by 1,4-butanediol and catalyzed by tin(II) bis 2-ethyl hexanoate (Sn(Oct) 2 ), followed by the quantitative esterification of hydroxyl end-groups by activated 4-pentynoic acid. In parallel, an azido-containing PDMAEMA-based copolymer was obtained in a three-step strategy involving primarily the copolymerization of DMAEMA with newly synthesized 2-(2-azidoethoxy)ethyl methacrylate (AEEMA) monomer. The latter was obtained by nucleophilic substitution of chloride atom from 2-(2-chloroethoxy)ethanol by an azide group followed by the esterification reaction of the hydroxyl group with methacrylic anhydride. The copolymerization was carried out in an equivolumic mixture of H 2 O and isopropanol at r.t. and initiated by a ω-bromoisobutyryl oligo PEO macroinitiator in the presence of various ligated copper(I)-based catalysts. In a last step, both polymer precursors were chemically linked by the Huisgen-1,3-dipolar cycloaddition in anhydrous THF at r.t. using CuBr complexed by 2,2'-bipyridine ligand as catalyst. Final material was characterized by the means of DSC and SEM, both attesting of a homogeneous distribution of the PCL crosslinkers and a highly porous structure in this new amphiphilic model conetworks.

First synthesis of 4,5-dihydro-3(2 H)-pyridazinones via Zn-mediated hydrohydrazination

The hydrohydrazination of 4-pentynoic acid with different arylhydrazines proceeds smoothly in the presence of zinc chloride. The domino amination–amidation sequence leads to aryl-substituted 4,5-dihydro-3(2 H)-pyridazinones.

Cu(I)-Catalyzed Intramolecular Cyclization of Alkynoic Acids in Aqueous Media: A “Click Side Reaction”

Alkynoic acids, in particular, 4-pentynoic acid derivatives, undergo intramolecular cyclizations to enol lactones under reaction conditions typically applied for the Cu(I)-catalyzed cycloaddition of terminal alkynes and azides (click chemistry). Starting from appropriate alkynoic acid derivatives, either enol lactones or 1,2,3-triazole click products can be obtained selectively by Cu(I) catalysis in aqueous media.

An Epoxidation Approach to a Chiral Lactone: Application of the Shi Epoxidation

The large-scale epoxidation of the alkene 7 with the organocatalyst, Epoxone (10), and Oxone as the oxidant is described. This is the first large-scale application of the Shi epoxidation methodology. The large-scale preparation of the catalyst 10 is also described. The potassium salt of the unsaturated acid precursor 7 was prepared by a Suzuki coupling from 3-fluorobenzyl chloride and the vinylborane 8 derived from 4-pentynoic acid.