Aliphatic Carboxylic Acid Esters Research Articles

Photoinduced Decarboxylative Radical Phosphinylation.

Reported herein is an unprecedented protocol for C(sp3 )-phosphinylation. With 1 mol % 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene) as the catalyst, the visible light induced reaction of redox-active esters of aliphatic carboxylic acids with dimethyl arylphosphonites or diethyl alkylphosphonites at room temperature provides the corresponding decarboxylative phosphinylation products in satisfactory yields. The protocol exhibits broad substrate scope and wide functional-group compatibility, enabling the late-stage modification of complex molecules and rapid synthesis of bioactive phosphinic acids such as glutamine synthetase phosphinothricin and a kynureninase inhibitor. A radical-polar crossover mechanism involving the formation and subsequent oxidation of phosphoranyl radicals followed by nucleophilic demethylation (or deethylation) is proposed.

Photoinduced Decarboxylative Radical Phosphinylation

AbstractReported herein is an unprecedented protocol for C(sp3)‐phosphinylation. With 1 mol % 4CzIPN (1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene) as the catalyst, the visible light induced reaction of redox‐active esters of aliphatic carboxylic acids with dimethyl arylphosphonites or diethyl alkylphosphonites at room temperature provides the corresponding decarboxylative phosphinylation products in satisfactory yields. The protocol exhibits broad substrate scope and wide functional‐group compatibility, enabling the late‐stage modification of complex molecules and rapid synthesis of bioactive phosphinic acids such as glutamine synthetase phosphinothricin and a kynureninase inhibitor. A radical‐polar crossover mechanism involving the formation and subsequent oxidation of phosphoranyl radicals followed by nucleophilic demethylation (or deethylation) is proposed.

Hemetsberger–Knittel and Ketcham Synthesis of Heteropentalenes with Two (1:1), Three (1:2)/(2:1) and Four (2:2) Heteroatoms

The synthetic methods leading to furo[3,2-b]pyrroles and thiazolo [5,4-d]thiazoles are reviewed herein. Furo-, thieno- and seleno [3,2-b]pyrroles are related to heteropentalenes, containing two heteroatoms in the entire structure, one each per core. The synthetic approach follows the Hemetsberger–Knittel protocol covering three reaction steps—the nucleophilic substitution of halogen-containing aliphatic carboxylic acid esters, Knoevenagel condensation and, finally, thermolysis promoting the intramolecular cyclocondensation to O,N-heteropentalene. The Hemetsberger–Knittel reaction sequence is also known for the preparation of O,N-heteropentalenes with three heteroatoms (2:1) and their sulphur and selen heteroatoms containing structural analogues and bispyrroles. The synthetic approach towards thiazolo [5,4-d] thiazoles represents a more straightforward route, according to the Ketcham cyclocondensation. Proceeding with the Ketcham process is more challenging since it occurs stepwise and the formation of by-products is obvious. Thiazolo [5,4-d]thiazole is a representative of the aromatic heteropentalene with four heteroatoms in the structure—twinned N and S, two for each of the five-membered rings. The synthetic approaches towards those particular heteropentalnes have been chosen as a consequence of our ongoing research dealing with the design, synthesis and applications of substituted furo [3,2-b]pyrroles and thiazolo [5,4-d]thiazole-based derivatives. While the furopyrroles are known for their pharmacological activity, thiazolothiazoles have become of interest to materials science. We are aware that from a “bank” of existing compounds/procedures not all are presented in this review, and we apologise to respective groups whose research have not been objectively included.

Photocatalytic Decarboxylative Coupling of Aliphatic N-hydroxyphthalimide Esters with Polyfluoroaryl Nucleophiles.

Polyfluoroarenes are an important class of compounds in medical and material chemistry. The synthesis of alkylated polyfluoroarenes remains challenging. Here we describe a decarboxylative coupling reaction of N‐hydroxyphthalimide esters of aliphatic carboxylic acids with polyfluoroaryl zinc reagents (Zn‐ArF) via synergetic photoredox and copper catalysis. This method readily converts primary and secondary alkyl carboxylic acids into the corresponding polyfluoroaryl compounds, which could have a wide range of F‐content (2F‐5F) and variable F‐substitution patterns on the aryl groups. Broad scope and good functional group compatibility were achieved, including on substrates derived from natural products and pharmaceuticals. Mechanistic study revealed that a [Cu‐(ArF)2] species could be responsible for the transfer of polyfluoroaryl groups to the alkyl radicals.

Photocatalytic Decarboxylative Coupling of Aliphatic N‐hydroxyphthalimide Esters with Polyfluoroaryl Nucleophiles

AbstractPolyfluoroarenes are an important class of compounds in medical and material chemistry. The synthesis of alkylated polyfluoroarenes remains challenging. Here we describe a decarboxylative coupling reaction of N‐hydroxyphthalimide esters of aliphatic carboxylic acids with polyfluoroaryl zinc reagents (Zn‐ArF) via synergetic photoredox and copper catalysis. This method readily converts primary and secondary alkyl carboxylic acids into the corresponding polyfluoroaryl compounds, which could have a wide range of F‐content (2F‐5F) and variable F‐substitution patterns on the aryl groups. Broad scope and good functional group compatibility were achieved, including on substrates derived from natural products and pharmaceuticals. Mechanistic study revealed that a [Cu‐(ArF)2] species could be responsible for the transfer of polyfluoroaryl groups to the alkyl radicals.

Catalytic Decarboxylative Radical Sulfonylation

Summary Sulfones are key structural motifs in pharmaceuticals and agrochemicals, and their synthesis is of paramount importance in organic chemistry. While nucleophilic and electrophilic C(sp3)-sulfonylation are well documented, radical C(sp3)-sulfonylation remains elusive. Herein, we report the decarboxylative radical sulfonylation with sulfinates. With the merger of 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene) and Cu(OTf)2 as catalysts, the visible-light-induced reaction of redox-active esters of aliphatic carboxylic acids with organosulfinates at room temperature provides the corresponding decarboxylative sulfonylation products in satisfactory yields. This redox-neutral protocol exhibits broad substrate scope and wide functional group compatibility, enabling the late-stage modification of complex natural products and bioactive pharmaceuticals. The synthetic utility of the method is further demonstrated by the improved synthesis of anti-prostate cancer drug bicalutamide. A mechanism involving sulfonyl group transfer from Cu(II)–SO2R to alkyl radicals is proposed.

Ruthenium Catalysts for Hydrogenation of Aromatic and Aliphatic Esters: Make Use of Bidentate Carbene Ligands

Committed carbenes: The convenient application of bidentate carbene ligands is described for the hydrogenation of carboxylic acid esters. The ligand precursors are easily synthesized through the dimerization of N-substituted imidazoles with diiodomethane. The catalyst is generated in situ and exhibits good activity and functional group tolerance for the hydrogenation of aromatic and aliphatic carboxylic acid esters.

The PE16 (Rv1430) of Mycobacterium tuberculosis Is an Esterase Belonging to Serine Hydrolase Superfamily of Proteins

The PE and PPE multigene families, first discovered during the sequencing of M. tuberculosis H37Rv genome are responsible for antigenic variation and have been shown to induce increased humoral and cell mediated immune response in the host. Using the bioinformatics tools, we had earlier reported that the 225 amino acid residue PE-PPE domain (Pfam: PF08237) common to some PE and PPE proteins has a “serine α/β hydrolase” fold and conserved Ser, Asp and His catalytic triad characteristic of lipase, esterase and cutinase activities. In order to prove experimentally that PE-PPE domain is indeed a serine hydrolase, we have cloned the full-length Rv1430 and its PE-PPE domain into pET-28a vector, expressed the proteins in E. coli and purified to homogeneity. The activity assays of both purified proteins were carried out using p-nitrophenyl esters of aliphatic carboxylic acids with varying chain length (C2–C16) to study the substrate specificity. To characterize the active site of the PE-PPE domain, we mutated the Ser199 to Ala. The activity of the protein in the presence of serine protease inhibitor- PMSF and the mutant protein were measured. Our results reveal that Rv1430 and its PE-PPE domain possess esterase activity and hydrolyse short to medium chain fatty acid esters with the highest specific activity for pNPC6 at 37°C, 38°C and pH 7.0, 8.0. The details of this work and the observed results are reported in this manuscript.

Antibacterial activity of bee propolis samples from different geographical regions of Turkey against two foodborne pathogens, Salmonella Enteritidis and Listeria monocytogenes

The aim of the present study was to investigate the antibacterial activities of 25 propolis samples collected from various geographical regions of Turkey against 2 food-borne pathogens, Salmonella Enteritidis ATCC 13076 and Listeria monocytogenes ATCC 1462. The chemical compositions of ethyl alcohol extracts of the propolis (EEP) samples were determined by gas chromatography coupled to mass spectrometry. The main components of EEP samples were flavonoids, aromatic acid esters, aromatic alcohols, aromatic acids, aliphatic carboxylic acids, terpens, and aliphatic carboxylic acid esters. Antibacterial activities of the EEP samples were tested at 2 different dilutions of 1:10 and 1:100 (v/v). All EEP samples at 1:10 dilution showed high antibacterial activity against the test bacterial strains and no viable bacteria were determined after incubation. The S. Enteritidis strain was found to be resistant toward EEP samples at 1:100 dilution ratios. However, most of the EEP at 1:100 dilution ratios had high antibacterial activity against the L. monocytogenes strain. While some of EEP at 1:100 dilution ratios killed all viable cells of L. monocytogenes, some EEP carried out 1-6 log reductions in the viable cells of this strain. Antibacterial activity of propolis depends on the chemical composition and types of bacteria. The propolis samples had a marked antibacterial action against the gram-positive strain and limited activity against gram-negative one depending on EEP concentration.

Structure and reactivity in the hydrolyses of aliphatic carboxylic acid esters and chlorides

AbstractFor hexanoic acid and its seven isomers, relative rates have been determined for acid catalysed esterification with methanol, and compared with those for saponification of the methyl esters. A good correlation between logarithms of relative rates for the two reactions is obtained, and it is suggested that the eight isomers provide a test set of compounds in which steric effects alone act on reactivity at the acyl carbon. A full set of steric parameters ($E_{\rm s}^\prime$ values) are presented. Rates of solvolyses of the acid chlorides of the isomers have been determined conductometrically in 3:1 wt:wt acetonitrile water. Logarithms of relative rates show a poor correlation with $E_{\rm s}^\prime$, and, taking into account the solvent dependence of the rates, the pattern excludes both rate‐limiting formation of a tetrahedral intermediate and rate‐limiting dissociation of chloride to form acylium ions. The remaining possibilities, a concerted process (AND) and rapid reversible formation of a hydrate followed by rate‐limiting dissociation of chloride (AN + D) are considered. Copyright © 2007 John Wiley & Sons, Ltd.

Stability and perfusion studies of Desmopressin (dDAVP) and prodrugs in the rat jejunum

Three aliphatic carboxylic acid esters of the tyrosine phenolic group in Desmopressin (dDAVP) were investigated in vitro for their stability and metabolism in rat gastrointestinal media. The degradation followed strictly first-order kinetics and the prodrugs were quantitatively converted to dDAVP. The n-hexanoyl (II) and n-octanoyl (III) esters were rapidly hydrolysed in 10% rat jejunal fluid showing half-lives of 1.1+/-0.2 min and 1.4+/-0.1 min, respectively. In 5 % rat jejunal homogenate the half-lives were 3.2+/-0.2 min and <30 sec, respectively. The sterically hindered pivalate ester (I) proved to be more stable. The half-lives were 10.3+/-0.3 min in 10% rat jejunal fluid and 1.5+/-0.1 min in 10% rat jejunal homogenate, respectively. The presence of paraoxon, an inhibitor of type B esterases significantly decreased the degradation rate of the pivalate ester (I) in rat jejunal fluid (t1/2 > 5 hrs) indicating that the prodrug is converted to dDAVP by rapid luminal breakdown of the ester bond. It was shown that approximately 13 % of prodrug I disappeared from the gut lumen during a single-pass perfusion experiment in rat jejunum. Our results indicate that the disappearance from the jejunal lumen was primarily caused by degradation of the prodrug to dDAVP by esterases rather than absorption. The better stability of the sterically hindered prodrug (I) indicate that even more sterically hindered prodrugs will be a better choice for a further optimization of stability and lipophilicity, and consequently a potentially improved intestinal absorption of dDAVP.

ChemInform Abstract: Kinetics and Mechanism of the Synthesis of Nitroethylene from Nitroethyl Esters of Aliphatic Carboxylic Acids.

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.

Preparation and evaluation of fatty acid esters of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole as fluorescent substrates for measurement of lipase activity.

A series of four aliphatic carboxylic acid esters (acetate, caproate, laurate and palmitate) of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDPI) was prepared. Usefulness of these esters as fluorescent substrates for the measurement of lipase activity was evaluated using a high performance liquid chromatographic method. The hydrolysate, HDPI, could be well separated from each substrate by a reversed-phase column and detected at 440 nm emission (cutoff-filter) with 360 nm excitation. Lipase from Candida cylindracea was used for the investigation. From their kinetic parameters, the caproate and laurate were found to be suitable for the lipase. Using the laurate, from 5 to 500 mU per assay tube of the lipase was determined.

Prodrugs of peptides. 18. Synthesis and evaluation of various esters of desmopressin (dDAVP).

Various aliphatic carboxylic acid esters and a carbonate ester of the tyrosine phenolic group in desmopressin were synthesized to assess their suitability as prodrugs with improved bioavailability compared to the parent peptide. The chemical stability of the esters in aqueous solution was similar to that of simple phenol esters. The derivatives were quantitatively converted to desmopressin by enzymatic hydrolysis in human plasma and rabbit liver homogenate. The esters with a straight side chain were rapidly hydrolyzed by alpha-chymotrypsin, but the sterically hindered pivalate ester proved more stable than desmopressin itself toward this proteolytic enzyme. All the esters were more lipophilic than desmopressin in terms of octanol-buffer partition coefficients. The transport of the compounds across confluent monolayers of Caco-2 cells was examined. No correlation between permeability and lipophilicity was found but the pivalate ester showed a markedly higher flux relative to desmopressin. It is concluded that appropriate esterification of desmopressin at its tyrosine group may be a potentially useful prodrug approach.

Species and Sex Specificity in the Odour Composition of Two Panurgine Bees (Hymenoptera, Andrenidae)

Abstract From the volatile constituents of the solitary bee species Panurgus banksianus Kirby and P. calcaratus Scopuli 31 compounds could be identified. The cephalic secretion of P. banksianus is a sex specific m ulticomponent mixture of terpenes and aliphatic carboxylic acid esters while P. calcaratus contains monoterpenes only. The major component in the Dufour’s gland secretion of P. banksianus is a macrocyclic lactone, eicosanolide, which is absent in P. calcaratus. In contrast, the new terpenoid ester, geranyl citronellate, is present in large amounts in the Dufour’s gland secretion of P. calcaratus.

Hydrolysis of Active Esters of Aliphatic Carboxylic Acids with Cyclic Dipeptide Catalysts Consisting of l-Histidine and Different Aliphatic α-Amino Acids

Abstract The hydrolyses of a series of p-nitrophenyl carboxylates with different acyl chains were investigated at 25 °C, pH 7.8 using cyclic dipeptides[cyclo(–l- or d-Xyz–His–) consisting of l-histidine (l-His) and an α-amino acid (Xyz) with different aliphatic side chains] as catalysts. Consequently, cyclo(–d-Leu–l-His–) and cyclo(–d-Val–l-His–) were found to be specifically effective catalysts for the hydrolysis of p-nitrophenyl laurate. These trans (d-l-type) cyclic dipeptides were much more efficient catalysts than their diastereomers, and were more reactive than imidazole, despite the fact that the former are less basic than the latter. The conformation of the cyclic peptides in solution was investigated using proton magnetic resonance spectroscopy and the relationship between conformation and catalytic activity was investigated. Consequently, it was found that the hydrophobic interaction between a catalyst and a substrate and the stereochemical fit for the cooperation of functional groups in the intramolecular nucleophilic catalysis are very important in order to attain a highly efficient catalysis. It was also found that the functional groups should have a certain size and flexibility in order to realize an effective stereochemical fit between functional groups of catalysts and substrates.

Temperature-dependence study of λ-CH Proton Couplings in radicals from aliphatic carboxylic acid esters

Earlier liquid-phase EPR measurements at room temperature of the λ-CH proton couplings in the CH(X 3(X 4)- groups of ·C(X 1)(X 2)OC(O)CH(X 3X 4) radicals and in the CH 2(X 1)- groups of CH 2(X 1)OC(O)C(X 2)(X 3) radicals (where an X- is an H- or a simple substituent such as CH 3-) together with comprehensive INDO-MO-SCF investigations on these same species have allowed the conformational preferences of these radicals to be deduced. The experimentally observed long-range λ-CH proton couplings in these species were demonstrated to be sensitive probes of variations in preferred radical conformation induced by steric and electronic effects of the alkyl substituents. The present paper shows that measurements of the temperature dependence of the λ-CH proton EPR coupling constants in these two types of radicals can be used successfully to determine their preferred conformations at room temperature. The conformations so obtained confirm those previously assigned using INDO-MO-SCF calculations.

Syngas reactions: V. Ethylene from synthesis gas

A new two-step process scheme for the production of ethylene from synthesis gas is proposed, wherein ethyl esters of aliphatic carboxylic acids are first generated directly from synthesis gas and the appropriate acid, through the use of homogeneous ruthenium catalysts coupled with quaternary phosphonium salt promoters. Pyrolysis of the isolated, intermediate ethyl ester yields ethylene and recyclable acid.

Glass capillary gas chromatography of homologous series of esters : IV. Separation of homologous series of certain halogenopropyl esters of aliphatic carboxylic acids on OV-101

Glass capillary gas chromatography of homologous series of esters : IV. Separation of homologous series of certain halogenopropyl esters of aliphatic carboxylic acids on OV-101

ChemInform Abstract: HOMOGENEOUS CATALYTIC HYDROGENATION OF CARBOXYLIC ACID ESTERS TO ALCOHOLS

AbstractDer aus (I) zugängliche anionische Rutheniumhydridkomplex (II) dient als homogener Katalysator bei der Reduktion der Ester (III) und (VII) zu den primären Alkoholen (IV) bzw. (VIII).