Phenylacetyl Derivatives Research Articles

Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation.

ChemInform Abstract: Enzymic Synthesis Design and Enzymic Synthesis of Aspartame.

Abstract An enzymic synthesis of aspartame (H-Asp-Phe-OMe) has been designed and realized based on the structure-activity study of thermolysin and penicillin amidase hydrolysis of its p-substituted phenylacetyl derivatives. These compounds meet the structural and energetic requirements of two enzymic binding sites The peptide sweetener has been prepared by thermolysin - catalyzed condensation of the p-substituted phenylacetyl-Asp-OH and H-Phe-OMe followed by penicillin amidase - catalyzed deprotection of the resulted aspartame precursors.

Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II

Based on a highly potent allophenylnorstatine-containing inhibitor, KNI-10006, against the plasmepsins of Plasmodium falciparum, we synthesized a series of tripeptide-type compounds with various N-terminal moieties and evaluated their inhibitory activities against plasmepsin II. Certain phenylacetyl derivatives exhibited extremely high affinity with K i values of less than 0.1 nM suggesting successful hydrophobic interactions.

Organic Derivatives of Alkylene Dithiophosphates, Part IV: Synthesis and Properties of Phenyl Acetyl and p-Methyl Benzoyl Derivatives of Alkylene Dithiophosphates

Reactions of phenyl acetyl chloride and p-methylbenzoyl chloride with ammonium salt of alkylene dithiophosphates in a 1:1 molar ratio in refluxing benzene solution yields nonvolatile dark yellow- or brown-colored viscous liquids of the type S 2 R (R = ─OCCH 2 C 6 H 5 , ─OCC 6 H 4 CH 3 , G = ─CMe 2 CMe 2 ─, ─CH 2 CH 2 CHMe─, ─CH 2 (CH 2 ) 2 CH 2 ─, and ─CMe 2 CH 2 CHMe─). The compounds thus obtained are hygroscopic and monomeric in nature. The newly synthesized compounds have been characterized by physicochemical and spectroscopic techniques (MW, IR, NMR [ 1 H & 31 P]).

Preparation and immunological studies of protein conjugates of N -acylneuraminic acids.

The overexpression of N -acetylneuraminic acid (Neu5Ac) is closely correlated with malignant transformations. Thus, Neu5Ac is an important target in the design of cancer vaccines. To study the influence of chemical modifications of Neu5Ac on its immunological properties, the alpha-allyl glycosides of five differently N -acylated neuraminic acid derivatives were prepared. Following selective ozonolysis of their allyl group to form an aldehyde functionality, they were coupled to keyhole limpet hemocyanin (KLH) via reductive amination. Resultant glycoconjugates were studied in C57BL/6 mice. The N -propionyl, N - iso- butanoyl and N -phenylacetyl derivatives of neuraminic acid provoked robust immune responses of various antibody isotypes, including IgM, IgG1, IgG2a and IgG3, whereas N -trifluoropropionylneuraminic acid and natural Neu5Ac were essentially nonimmunogenic. Moreover, the N -phenylacetyl and N - iso- butanoyl derivatives mainly induced IgG responses that are desirable for antitumor applications. These results raise the promise of formulating effective glycoconjugate cancer vaccines via derivatizing sialic acid residues of sialooligosaccharides.

ChemInform Abstract: Synthesis and Biological Evaluation of Phenylacetyl Derivatives Having Low Central Nervous System Permeability as Potent and Selective M2 Muscarinic Receptor Antagonists.

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Synthesis and Biological Evaluation of Phenylacetyl Derivatives Having Low Central Nervous System Permeability as Potent and Selective M2 Muscarinic Receptor Antagonists.

A series of phenylacetyl derivatives containing the 5,10-dihydro-11H-dibenzo[b,e,][1,4]diazepin-11-one or 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton was prepared and evaluated for their binding affinities to muscarinic receptors in vitro and for antagonism of bradycardia, salivation and tremor in vivo. Among them, compounds 56 and 66 had high affinity for M2 muscarinic receptors in the heart (pKi = 8.7 and 8.9, respectively) with low affinity for M3 muscarinic receptors in the submandibular gland. A structure-activity relationship (SAR) study suggested that the high M2 selectivity over the M3 muscarinic receptors of 56 may be attributed to the direction of the carboxamide carbonyl group. In in vivo studies, 56 and 66 antagonized oxotremorine-induced bradycardia in rats on both intravenous and oral administration, and their heart rate increasing effect in dogs with nocturnal bradycardia was about 3-fold greater than that of AF-DX 116. Furthermore, they had almost no influence on oxotremorine-induced tremor in mice, presenting no evidence of central transfer.

N-Protection of Amino Acid Derivatives Catalyzed by Immobilized Penicillin G Acylase

The introduction of a N-α-phenylacetyl moiety into glycine, methionine and aspartic acid derivatives using immobilized penicillin G acylase (PGA) as catalyst was studied. High synthetic yields (86–97%) were obtained in biphasic systems under thermodynamic control using fully carboxy-protected derivatives of amino acids such as H-Gly-OMe, H-Gly-OBzl, H-Met-OEt, H-Asp(OBut)-OMe, H-Asp(OMe)-OMe and H-Asp(OBzl)-OBzl. Moderate yields (50–62%) were obtained for the N-α protection of β-carboxy free, α-carboxy esters of aspartic acid such as H-Asp-OMe and H-Asp-OBzl in methanol/buffer mixtures under kinetic control. The synthesis of some phenylacetyl derivatives on a preparative scale under the optimum conditions is also described.

Penicillin amidase-catalysed transfer of low specific acyl moiety. Synthesis of 7-benzoxazolonylacetamido desacetoxycephalosporanic acid

The methyl ester of 2-benzoxazolon-3-yl-acetic acid was used as an acyl donor in the penicillin amidase-catalysed transfer reaction to 7-aminodesacetoxycephalosporanic acid. The synthesis of 7-(2-benzoxazolon-3-yl-acetamido)-desacetoxycephalosporanic acid was carried out as a kinetically controlled reaction. A characteristic feature of this system is that the benzoxazolone derivatives are very low specific substrates for penicillin amidase (the k cat K m values for their hydrolysis were shown to be 10 5-fold lower compared to the corresponding values for phenylacetyl derivatives). Nevertheless, penicillin amidase proved to be an effective catalyst for the synthesis of these new cephem derivatives (50% yield for 6 h). The reason is the observed unusually high value for the transferase-hydrolase activity ratio. The determined value for ( k′ 3 k 3 ) app = 120,000 implies that in this case of low specific acyl moiety, penicillin amidase acts more like a transferase than a hydrolase. The maximum yield has been increased up to 70% by lowering the reaction temperature and stepwise feeding of the reaction medium with the acyl component. The results obtained extend the potential of the penicillin amidase as a catalyst for the synthesis of a new group of biologically active cephem derivatives.

Enzymic synthesis design and enzymic synthesis of aspartame

An enzymic synthesis of aspartame (H-Asp-Phe-OMe) has been designed and realized based on the structure-activity study of thermolysin and penicillin amidase hydrolysis of its p-substituted phenylacetyl derivatives. These compounds meet the structural and energetic requirements of two enzymic binding sites The peptide sweetener has been prepared by thermolysin - catalyzed condensation of the p-substituted phenylacetyl-Asp-OH and H-Phe-OMe followed by penicillin amidase - catalyzed deprotection of the resulted aspartame precursors.

Penicillin acylase-catalyzed protection and deprotection of amino groups as a promising approach in enzymatic peptide synthesis

Penicillin acylase from E. coli is able to catalyze both the introduction and the removal of the phenylacetyl group. We have established that phenylacetyl derivatives of amino acids and peptides can be used in protease-catalyzed peptide synthesis. Here the synthesis of leucine-enkephalin using enzymes for N-terminal amino group protection, peptide bond formation and deprotection is described.

Optical resolution of methionine and .EPSILON.-N-benzoyl-lysine by metabolism of Escherichia coli on phenylacetyl derivatives.

Optical resolution of methionine and .EPSILON.-N-benzoyl-lysine by metabolism of Escherichia coli on phenylacetyl derivatives.

Soviet note of protest, March 15

The methyl ester of 2-benzoxazolon-3-yl-acetic acid was used as an acyl donor in the penicillin amidase-catalysed transfer reaction to 7-aminodesacetoxycephalosporanic acid. The synthesis of 7-(2-benzoxazolon-3-yl-acetamido)-desacetoxycephalosporanic acid was carried out as a kinetically controlled reaction. A characteristic feature of this system is that the benzoxazolone derivatives are very low specific substrates for penicillin amidase (the kcatKm values for their hydrolysis were shown to be 105-fold lower compared to the corresponding values for phenylacetyl derivatives). Nevertheless, penicillin amidase proved to be an effective catalyst for the synthesis of these new cephem derivatives (50% yield for 6 h). The reason is the observed unusually high value for the transferase-hydrolase activity ratio. The determined value for (k′3k3)app = 120,000 implies that in this case of low specific acyl moiety, penicillin amidase acts more like a transferase than a hydrolase. The maximum yield has been increased up to 70% by lowering the reaction temperature and stepwise feeding of the reaction medium with the acyl component. The results obtained extend the potential of the penicillin amidase as a catalyst for the synthesis of a new group of biologically active cephem derivatives.

Phenylacetyl Derivatives of Methylhydrazine1

Phenylacetyl Derivatives of Methylhydrazine¹

微生物に於けるアシラーゼ能の研究 (第3報)

The acylase of soil bacteria KT 84 was extracted in a cell-free state and its cell-free acetone powder was prepared.The bacterial mass, acetone-dried powder, cell-free extract, and cell-free acetone powder of KT 84 all effected asymmetric hydrolysis of α, ε-di-N-benzoyl- and α-N-acetyl-ε-N-benzoyl-DL-lysine affording ε-N-benzoyl-L-lysine and α, ε-di-N-benzoyl-D-lysine, and ε-N-benzoyl-L-lysine and α-N-acetyl-ε-N-bezoyl-D-lysine, respectively. The benzoyl derivative of ε-N-benzoyl-L-lysine was more easily hydrolysed than its acetyl derivative in this case.Eleven kinds of α-N-acyl derivative of ε-N-benzoyl-DL-lysine were synthesized and hydrolytic action of cell-free extract of KT 84 was examined by ninhydrin colorimetry. The results showed that (1) m- and p-nitrobenzoyl, dichloroacetyl, and benzoyl derivatives were more easily hydrolyzed than other acyl derivatives; (2) m- and p-nitrobenzoyl derivatives were hydrolyzable but o-nitrobenzoyl was hardly hydrolyzed, while p-aminobenzoyl was far more resistant to hydrolysis than p-nitrobenzoyl derivative; (3) cinnamoyl and phenylacetyl derivatives are less hydrolyzable than benzoyl derivative; and that (4) chloroacetyl, acetyl, and formyl derivatives are much less hydrolyzable than dichloroacetyl derivative.