Bioactive Carboxylic Acids Research Articles

Direct α-Trifluoromethylthiolation of Carboxylic Acids Enabled by Boron Catalysis

AbstractA boron-catalyzed direct α-trifluoromethylthiolation of carboxylic acids was developed. Catalytically generated boron enediolates reacts with electrophilic SCF3 reagent, N-SCF3-phthalimide, to provide α-SCF3 carboxylic acids without the need of substrate pre-activation. The method is applicable to direct modification of bioactive carboxylic acids. Data science analyses provided suitable models for substrate classification as well as yield prediction.

Direct 3-Acylation of Indolizines by Carboxylic Acids for the Practical Synthesis of Red Light-Releasable Caged Carboxylic Acids.

To enhance the practicality of photouncaging system using 3-acyl-2-methoxyindolizines, direct acylation of indolizines with carboxylic acids was developed using condensation reagents, generally used for peptide coupling. This method allowed for caging a broad range of carboxylic acids with indolizines. The method enabled a facile synthesis of water-soluble caged bioactive carboxylic acids having an intramolecular photosensitizer. The efficient release of carboxylic acids from the synthesized caged compounds upon red light irradiation was confirmed in neutral buffered solutions.

Visible-Light-Mediated Decarboxylative Radical Addition Bifunctionalization Cascade for the Production of 1,4-Amino Alcohols.

A photocatalytic decarboxylative radical addition bifunctionalization cascade for the synthesis of functionalized alcohols is described. The catalytic cycle is completed through single-electron transfer. The advantages of this reaction are the commercially available materials, wide functional group compatibility, and mild conditions. Notably, some amino acids and bioactive carboxylic acids can provide corresponding products in moderate to good yields, reflecting the potential value in drug development.

Palladium-Catalyzed N-Acylation of Tertiary Amines by Carboxylic Acids: A Method for the Synthesis of Amides.

A palladium-catalyzed N-acylation of tertiary amines by carboxylic acids was achieved through C-N cleavage. This reaction showed a wide substrate scope. Both aromatic and aliphatic acids served well as the acylating reagents and coupled with tertiary amines to produce the corresponding amides in good to excellent yields. With the strategy, bioactive carboxylic acids were also efficiently modified, highlighting the synthetic value of the process in organic synthesis.

Synthesis and spectroscopic/DFT structural characterization of coordination compounds of Nb(V) and Ti(IV) with bioactive carboxylic acids

The reactions are reported of NbX5 (X = Cl, Br), TiCl4 and Ti(OiPr)4 with a selection of carboxylic acids exhibiting a known biological role, in a chlorinated solvent. The reactions of NbX5 with acetylsalicylic acid (aspirin) proceeded with selective deacetylation of the organic reactant and formation of the salicylate complexes NbX4(C7H5O3) (1a, X = Cl; 1b, X = Br) in 60–65% yields. NbCl5 reacted with diclofenac and ethacrynic acid (EA-CO2H) to give NbCl3[κ3O,O,N-O2CCH2(C6H4)NC6H3Cl2], 2 (80% yield), and NbCl4(O2C-EA), 3 (72% yield), respectively. Ti(OiPr)4 reacted with ethacrynic acid giving Ti(OiPr)2(O2C-EA)2, 4, in 74% yield, as a mixture of two isomers. All the products were characterized by means of analytical and spectroscopic methods, moreover DFT studies were carried out to give insight into structural features.

Photolytic release of bioactive carboxylic acids from fused pyran conjugates

New ester cages bearing the coumarin (2H-benzopyran-2-one) skeleton with extended π-systems as phototriggers, for glycine and β-alanine, as models of carboxylic acid bifunctional molecules with biological relevance, were evaluated under photolysis conditions at 254, 300, 350 and 419 nm of irradiation in a RPR-100 photochemical reactor. The processes were followed by HPLC-UV detection and 1H NMR with collection of kinetic data. The results showed a correlation between the photolysis efficiency and the increasing extension of the conjugation for both glycine and β-alanine, showing that the 7-aminocoumarin afforded the best results at all wavelengths tested.From a study of the time-resolved fluorescence behaviour, these compounds were also found to exhibit more complex fluorescence decay kinetics. This was attributed to the presence of conjugated and non-conjugated coumarin species.

A general strategy to add diversity to ruthenium arene complexes with bioactive organic compounds via a coordinated (4-hydroxyphenyl)diphenylphosphine ligand.

Esterification of (4-hydroxyphenyl)diphenylphosphine, coordinated to the [Ru(η6-p-cymene)Cl2] fragment, allows a series of bioactive carboxylic acids to be introduced directly into the organometallic molecule. Evaluation of the compounds on human ovarian cancer cells reveals synergistic enhancements in their antiproliferative activity relative to their bioactive organic and organometallic precursors.

Conformation specific and charge directed reactivity of radical cation intermediates of α-substituted (amino, hydroxy, and keto) bioactive carboxylic acids

The reactivity of radical cation carboxylic acids is investigated on the basis of mass spectrometry, infrared-vacuum ultraviolet (IR-VUV) photoionization spectroscopy, and high level correlated ab initio calculations. Their reactivity is found to be highly conformation specific and is governed by their initial charge distribution following ionization. In the present work, the radical cations of lactic acid, pyruvic acid, glycine, and valine are studied to probe their stability and conformation specific reactivity following single photon, vertical ionization at 10.5 eV. For lactic acid, glycine, and valine, the localization site of the hole following sudden removal of an electron depends on their specific intramolecular hydrogen bonding network. Lactic acid, glycine, and valine undergo complete fragmentation following vertical ionization at 10.5 eV; however, pyruvic acid does not completely dissociate following vertical ionization. Only 45% of the pyruvic acid parent ions undergo C(alpha)-C(carboxylic) bond dissociation. If the hole is localized on the COOH moiety of glycine, valine, and lactic acid, a hydrogen transfer is favored from the COOH to the alpha-substituent. If the hole is localized on the alpha-hydroxy or -amine substituent and the singly occupied molecular orbital (SOMO, where the hole resides) is parallel to the C(alpha)-C(carboxylic) bond, C(alpha)-C(carboxylic) bond dissociation occurs through charge transfer from the alpha-substituent to the C(alpha)-C(carboxylic) bond. The present study reveals that the specific conformations of alpha-substituted carboxylic acids govern their radical cationic reactivity. The radical cation of pyruvic acid exhibits a special stability due to enolization of the alpha-keto form on the cationic surface.

Synthesis and controlled release behaviour of dextran bioactive esters by direct reaction of dextran with the potassium salts of bioactive carboxylic acids

AbstractThis work deals with the coupling of model bioactive carboxylic acids (1‐naphthylacetic acid, 2‐(6‐methoxy‐2‐naphthyl)propionic acid (naproxen) and nicotinic acid) to dextran by direct reaction with their potassium salts using pyridine/sulfonyl chloride as activating agent. The structure of the resulting polymeric derivatives was determined by means of 1H and 13C NMR spectroscopy. The influence of the pyridine concentration, the type of sulfonyl chloride and the temperature on the reaction of dextran with potassium 1‐naphthyl acetate was evaluated. The activation energy was found to be 65,7 kJ/mol. 13C NMR spectra at 75,4 MHz of partially modified dextran with 1‐naphthyl acetate groups were studied in order to evaluate the selectivity of the reaction between dextran and potassium 1‐naphthyl acetate. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of the individual hydroxyl groups decreases in the order C2 > C4 > C3. The hydrolysis in the heterogeneous phase of some dextran polymers partially modified with 1‐naphthyl acetate groups shows that the release of the bioactive compound is dependent on the hydrophilic character of the polymer as well as the pH value of the medium.

Preparation of dextran-bioactive compound adducts by the direct esterification of dextran with bioactive carboxylic acids

The direct esterification reaction of dextran with α-naphthylacetic acid (a model bioactive carboxylic acid) is studied in homogeneous phase using pyridine-sulfonyl chloride as catalyst. The structure of the resulting adducts was determined by means of infra-red, 1H nuclear magnetic resonance (n.m.r.) and 13C n.m.r. spectroscopy. The influence of the pyridine concentration, the type of the sulfonyl chloride as well as the temperature was evaluated. Direct esterification reaction was also performed with other bioactive carboxylic acids, such as naproxen and nicotinic acid. 13C n.m.r. spectra at 75.4 MHz of partially modified dextran with α-naphthylacetate groups were studied in order to evaluate the selectivity of the reaction between dextran and α-naphthylacetic acid. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of the individual hydroxyl groups decreases in the order C2 > C4 > C3. On the basis of these results a probable mechanism for the reaction is suggested.

Poly(vinyl alcohol) functionalized by chloroacetate groups. Coupling of bioactive carboxylic acids

AbstractPoly(vinyl alcohol) (PVAL) functionalized with chloroacetate groups was obtained by reaction of PVAL with chloroacetyl chloride using pyridine as catalyst and N‐methyl‐2‐pyrrolidone as solvent. The structure of the modified polymers was determined by means of IR, 1H and 13C NMR spectroscopies. The coupling of model bioactive carboxylic acids (1‐naphthylacetic acid and 6‐methoxy‐α‐methyl‐2‐naphthaleneacetic acid (naproxen)) to PVAL functionalized with chloroacetate groups was carried out by reaction with their potassium salts or directly in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). High degrees of modification were obtained in the reaction with the potassium salts. However, the esterification reaction is somewhat more efficient in the case of the potassium salt of 1‐naphthylacetic acid. The kinetic results were consistent with a second‐order reaction, and the activation energy in the reaction with the potassium salt of 1‐naphthylacetic acid was found to be 73,2 kJ/mol. The reaction of PVAL with 1‐naphthylacetic acid and naproxen in the presence of DBU showed deviation from second‐order kinetics, which may be a consequence of some steric effects. The hydrolysis in the heterogeneous phase of PVAL‐1‐naphthylacetic acid and PVAL‐naproxen adducts showed that the release of the bioactive compound from tablets is dependent on the hydrophilic character of the adduct as well as on the pH value of the medium.

Functionalization of dextran with chloroacetate groups: immobilization of bioactive carboxylic acids

Dextrans partially functionalized with chloroacetate groups were obtained by reaction of dextran with chloroacetyl chloride using pyridine as catalyst and the dimethylformamide/LiCl system as solvent. The structure of the resulting polymers was determined by means of infra-red, 1H and 13C nuclear magnetic resonance (n.m.r.) spectroscopy. 13C n.m.r. spectra at 75.4 MHz of partially modified dextran with chloroacetate groups were studied in order to evaluate the selectivity of the reaction of dextran with chloroacetyl chloride in the homogeneous phase. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of the individual hydroxyl groups decreases in the order C2 > C3 > C4. The coupling of model bioactive carboxylic acids (α-naphthylacetic and 6-methoxy-α-2-naphthaleneacetic (naproxen)) to dextran functionalized with chloroacetate groups was carried out by reaction with their potassium salts or directly in the presence of 1,8-diazabicyclo[5.4.0]-7-undecene. High degrees of modification were obtained by both methods. However, the esterification reaction is somewhat more efficient in the case of the potassium salts.