Phenylacetic Acid Esters Research Articles

Enantioselective alpha-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3.

Here we report that an engineered microbial cytochrome P450 BM-3 (CYP102A subfamily) efficiently catalyzes the alpha-hydroxylation of phenylacetic acid esters. This P450 BM-3 variant also produces the authentic human metabolite of buspirone, R-6-hydroxybuspirone, with 99.5% ee.

A facile, KF/Al 2O 3 mediated method for the preparation of functionalized pyrido[2,3- d]pyrimidin-7(8 H)-ones

A series of functionalized pyrido[2,3- d]pyrimidin-7(8 H)-ones were prepared by a KF/Al 2O 3 mediated condensation of 4-(alkylamino)-2-(methylthio)pyrimidine-5-carbaldehydes and phenyl acetic acid ester derivatives.

On the formation of 4-[ N,N-bis(2-chloroethyl)amino]phenyl acetic acid esters of hecogenin and aza-homo-hecogenin and their antileukemic activity

The p-[ N,N-bis(2-chloroethyl)amino]phenylacetic acid esters of hecogenin and aza-homo-hecogenin have been prepared and their antineoplastic activity was evaluated against two basic drug screening systems in rodents, P388 lymphocytic and L1210 lymphoid murine leukemias. Among the compounds tested, the p-[ N,N-bis(2-chloroethyl)amino]phenylacetic acid ester of aza-homo-hecogenin was appeared to possess a significant higher antileukemic effect. These results support that the alkylating esters of hecogenin produce important antitumor activity as well as, indicate that the aza-homo-hecogenin ester exhibits significantly higher activity due to lactam group (–NHCO–) modification.

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to: Flavouring Group Evaluation 14 (FGE.14): Phenethyl alcohol, aldehyde, esters, and related phenylacetic acid esters from ch

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to: Flavouring Group Evaluation 14 (FGE.14): Phenethyl alcohol, aldehyde, esters, and related phenylacetic acid esters from ch

FUNGAL FORMATION OF RASPBERRY KETONE DIFFERS FROM THE PATHWAY IN PLANT CELL CULTURE

Various precursor substances for the biosynthesis of raspberry ketone were applied to the white rot fungus N. niveo-tomentosa to enhance product yields. L-Phenylalanine, phenyl pyruvate, phenyl propanoic acid, L-tyrosine, 4-hydroxyphenyl pyruvate, coumaric acid, 4-hydroxyphenyl propanoic acid, benzoic acid, hippuric acid, benzaldehyde, and 4-hydroxy benzaldehyde showed precursor activity, whilst cinnamic acid, phenyl acetic acid, phenyl acetaldehyde, and 4-hydroxybenzoic acid methyl ester inhibited fungal growth and/or formation of target compounds. Gas chromatography coupled with atomic emission detection (GC-AED) was used to elucidate the biosynthetic pathway to raspberry ketone after addition of 2H and 13C isotope labeled L-phenylalanine. Metabolic differences to the biosynthesis proposed for raspberry fruit became evident.

High hopanoid/total lipids ratio in Frankia mycelia is not related to the nitrogen status.

Vesicles are specific Frankia structures which are produced under nitrogen-limiting culture conditions. Hopanoids are the most abundant lipids in these vesicles and are believed to protect the nitrogenase against oxygen. The amounts and quality of each hopanoid were estimated in different Frankia strains cultivated under nitrogen-depleted and nitrogen-replete conditions in order to detect a possible variation. Studied Frankia strains nodulating Eleagnus were phylogenetically characterized by analysis of the nifD-K intergenic region as closely related to genomic species 4 and 5. Phylogenetically different strains belonging to three infectivity groups were cultivated in the same medium with and without nitrogen source for 10 d before hopanoid content analysis by HPLC. Four hopanoids together accounted for 23-87% and 15-87% of the total lipids under nitrogen-replete and nitrogen-depleted culture conditions, respectively. Two of the hopanoids found, bacteriohopanetetrols and their phenylacetic acid esters, have previously been described in Frankia Two new hopanoids, moretan-29-ol and a bacteriohopanetetrol propionate, have also been identified. The moretan-29-ol and bacteriohopanetetrols were found to be the most abundant hopanoids whereas the bacteriohopanetetrol propionate and phenylacetates were present at a concentration close to the limit of detection. The ratio of (bacteriohopanetetrols + moretan-29-ol)/(total lipids) varied in most of the strains between nitrogen-depleted and nitrogen-replete culture conditions. In most of the strains, the hopanoid content was found to be slightly higher under nitrogen-replete conditions than under nitrogen-depleted conditions. These results suggest that remobilization, rather than neosynthesis of hopanoids, is implicated in vesicle formation in Frankia under nitrogen-depleted conditions.

Unexpected Truce–Smiles type rearrangement of 2-(2′-pyridyloxy) phenylacetic esters: synthesis of 3-pyridyl-2-benzofuranones

Enolization of 2-(2′-pyridyloxy)phenylacetic acid esters with either potassium or sodium hydride induced a Truce–Smiles rearrangement, producing pyridine substituted 2-benzofuranones. Rearrangement of a 2-(4-nitrophenoxy)phenylacetate and a 2-(2′-pyrimidyloxy)phenylacetate produced similar results.

Enantioselective synthesis of 2,3-diphenyl-1,4-butanediol via oxidative coupling of phenylacetic acid chiral 1,1′-bi-2-naphthyl ester using TiCl 4/Et 3N

Oxidative coupling of phenylacetic acid ester of homochiral 1,1′-bi-2-naphthol 2 was achieved by reaction with TiCl 4/Et 3N to obtain the corresponding 2,3-diphenylsuccinic acid derivative 3, which on reduction using the NaBH 4/I 2 reagent gives homochiral 2,3-diphenyl-1,4-butanediol. X-Ray structural analysis was carried out for the compounds ( R)-(+)- 2 and ( R,R,R)-(−)- 3.

A new method for the determination of the absolute stereochemistry of aromatic and heteroaromatic alkanols using Mosher's esters

A list of the 1H NMR chemical shifts of the methoxy group of α-methoxy-α-(trifluoromethyl)phenylacetic acid (Mosher's) esters of α- and β-(hetero)aromatic secondary alkanols has been compiled. Methoxy groups which are orientated syn to the (hetero)aromatic group in Mosher's conformational model have lower chemical shift values than those in the anti-orientation.

A facile entry to l‐aryl‐4,5‐dihydro[1,4]oxazepino‐[5,4‐a]isoindole‐2,7‐diones

AbstractThe titled compounds were prepared by reacting N‐(2‐bromoethyl)phthalimide with enolates of phenylacetic acid esters. 2,3‐Dihydrooxazolo[2,3‐a]isoindolones are believed to be intermediates in the process. An X‐ray crystallographic analysis was conducted on one of the compounds.

Absolute Configuration of 2,6-Dimethylheptyl Sulfate and Its Distribution in Ascidiacea

2,6-Dimethylheptyl sulfate (1) was isolated for the first time from a marine ascidian from Policitor adriaticus Drasche (class Ascidiacea, order Aplousobranchiata, family Polycitoridae). In this work, the absolute stereochemistry at C-2 of 1 was determined by 1H-NMR analysis of its (+)- and (−)-methoxy(trifluoromethyl)phenylacetic acid (MTPA) esters (Mosher's method). The distribution of 1 was investigated among the three orders (Aplousobranchiata, Phlebobranchiata, and Stolidobranchiata) of the class Ascidiacea. Compound 1 showed cytotoxicity (LC50 = 17.8 μg/mL) in the Artemia salina bioassay and was not toxic (not toxicity at 100 μg/mL) in a fish (Gambusia affinis) lethality assay.

In vitro and in vivo suppression of gluconeogenesis by inhibition of pyruvate carboxylase

The mechanism of inhibition of gluconeogenesis by phenylalkanoic acids was studied in vitro and in vivo. In vitro production of 14CO 2 from labeled glucose or palmitate was not inhibited at 4 mM, a concentration of phenylacetic acid that inhibited gluconeogenesis from lactate/pyruvate. In vitro studies with isolated mitochondria showed that the CoA ester of phenylacetic acid was formed. The parent phenylalkanoic acid had no effect on purified pyruvate carboxylase activity, but phenylacetyl CoA ester decreased pyruvate carboxylation in a concentration-dependent manner. Phenylacetic acid inhibited gluconeogenesis in isolated rat liver cells from 10 mM lactate/1 mM pyruvate (decreased 39%, P < 0.05), but not 10 mM l-glutamine or [ 14C]aspartate, showing that the inhibition of gluconeogenesis occurred at the level of pyruvate carboxylase. A 20 mg bolus with infusion of 1 mg/min of phenylpropionic acid decreased blood glucose levels of normal [110 ± 12 to 66 ± 11 mg/dL, N = 7, P < 0.05 (unpaired Student's t-test vs control)] and streptozocin diabetic rats [295 ± 14 to 225 ± 12 mg/dL, N = 7, P < 0.01 (paired t-test vs basal)]. Hepatic glucose production in control and diabetic rats was suppressed under conditions where liver glycogen was depleted, indicating that gluconeogenesis had been inhibited in vivo. The results suggest the possibility that the inappropriate overproduction of glucose can be controlled by inhibitors of pyruvate carboxylase. This class of inhibitors may be useful in the treatment of non-insulin-dependent diabetes mellitus.

Dependence of the Reactivities of Titanium Enolates on How They Are Generated: Diastereoselective Coupling of Phenylacetic Acid Esters Using Titanium Tetrachloride.

Oxidative coupling of phenylacetic acid esters was easily achieved by treating the esters with TiCl(4) and then adding Et(3)N to the resulting solution. The products consisted of dl- and meso-2,3-diphenylsuccinic acid esters with the Claisen condensation product, and the ratio of these products depended on the reaction conditions. Reaction conditions suitable for high dl selectivity were determined, and a dimer of titanium enolate was postulated as an intermediate responsible for the high dl selectivity. The selectivities were compared with those in known oxidative couplings in which titanium enolate intermediates are prepared through lithium enolates and silyl enol ethers. The results suggest that the reactivities of titanium enolates intermediates depend on how they are generated.

Synthetic and mechanistic aspects of anionic polymerization of (METH)acrylates initiated by metal‐free salts of CH‐acidic compounds

AbstractThe tetrabutylammonium salts of CH‐acidic compounds (malonic acid diesters and diamides, nitropropane, phenylacetic and phenylpropionic acid esters and 9‐ethyltfuorene) serve as inexpensive initiators for the anionic polymerization of acrylates and methacrylates at room temperature. Molecular weights of 1500–25,000 can be reached, the molecular weight distributions being fairly narrow (D = 1·1–1·4 in optimized cases). Side‐reactions as monitored by GC analyses include backbiting and Hofmann elimination, which means that the process is not a true living polymerization. The x‐ray structural analyses of the tetrabutylammonium salts of phenylacetic and 2‐phenylpropionic and 2‐phenylbutyric acid esters show that anions and cations interact with one another via hydrogen bonding. Therefore, the initiators cannot be considered to be naked anions, a conclusin which very likely also applies to the growing polymer chain end during polymerization.

Structure, stereochemistry, and thermal isomerization of the male sex pheromone of the longhorn beetle Anaglyptus subfasciatus.

Male-released sex pheromone constituents of the longhorn beetle Anaglyptus subfasciatus (Coleoptera: Cerambycidae) are identified by GC-MS and GC-Fourier transform infrared as a 7:1 molar mixture of 3-hydroxy-2-hexanone and 3-hydroxy-2-octanone. These two compounds undergo thermal isomerization during GC analyses to give the corresponding 2-hydroxy-3-alkanones. Comparison of GC retention times of the natural products with those of synthesized enantiomerically pure compounds revealed that both semiochemicals have (R)-stereochemistry. These absolute configurations were confirmed by comparisons of the (R)-methoxy(trifluoromethyl)phenylacetic acid esters of insect-derived and synthetic samples.

Spectroscopy and Photochemistry of Phenylacetic Acid Esters and Related Substrates. The Stereoelectronic Dependence of the Aryl/Carboxyl Bichromophore Interaction

The 254-nm-initiated Norrish Type II photofragmentation of the ethoxyethyl esters of a series of phenylacetic acids (1b-4b) has been studied in order to further elaborate the aryl/ester interaction that is photochemically and photophysically evident in these systems. The ethoxyethyl ester of benzonorbornene-1-carboxylic acid (5) has also been prepared and studied, as has a rigid tricyclic lactone (6) which places the chromophores in an optimal stereoelectronic relationship for interaction. The experimental work is accompanied by Hartree-Fock (HF), Natural Bond Orbital (NBO), and Configuration Interaction with Single Excitations (CIS) calculations on the methyl esters of phenylacetic acid (1a) and α-methoxyphenylacetic acid (4a)

Stereoselectivity in the hydrolysis of synthetic esters by cultured cancer cells and normal tissue extracts of rat

Racemic 2-substituted phenylacetic acid esters and the related esters were hydrolyzed in different stereoselectivity by rat cancer cells and the corresponding rat normal tissue extracts. The stereoselectivity was dependent on the structure off the α-substituents.

Stereochemical differences in the michael addition of phenylacetic acid esters and dialkyl amides to methyl cinnamate or methyl crotonate

The stereochemistry of the conjugate addition of phenylacetic acid esters and dialkylamides to methyl crotonate is studied. The stereochemical results are compared with these previously obtained for the addition to methyl cinnamate. The differences observed are explained in terms of cyclic transition states with decreasing of the sterical interactions as a result of replacement of a phenyl group by methyl in position 2 of the 1,2-diphenylpropanic skeleton.

Mono- and bis(aminomethyl)phenylacetic acid esters as short-acting antiarrhythmic agents. 2.

The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrrolidinomethyl)-4-hydroxyphenylacetic acid series, the 1,4-benzodioxanyl-2-methyl(3q) and the thienyl-2-methyl(31) esters were evaluated in vivo for antiarrhythmic efficacy. In addition, a number of monoappended phenylacetic esters of 3q with or without the 4-hydroxy group were also prepared for evaluation of antiarrhythmic, lipophilic, and metabolic properties. Of these compounds, 3q possessed the most desirable pharmacological and pharmacokinetic profile.

7-O-Methyl-luteone Metabolism in Botrytis cinerea: Identification of the Epoxy-Intermediate and Absolute Configuration of the Pyrano-isoflavone Metabolite

7-O-Methyl-luteone was metabolized in a buffer solution by resting cells of Botrytis cinerea which is known as a fungus detoxifying prenylated isoflavones into further oxygenated metabolites, and we could isolate an unstable epoxy-intermediate. The epoxy-intermediate was easily cyclized under acidic conditions to yield the corresponding isoflavone with a hydroxychroman part structure (= dihydropyrano-isoflavone). The optically active (dextrorotatory) dihydropyrano-isoflavone metabolite was derivatized into the [R]-a-methoxy-a-trifluoromethyl- phenylacetic acid ester and its absolute configuration [S] was unambiguously elucidated by the modified Mosher’s method.