N-acetyl Compounds Research Articles

The metabolism of S-carboxyalkylcysteines in man.

1. The ingestion of S-(2-carboxy-1-methylethyl)-, S-(2- carboxy-1-methylpropyl)-, S-(1-carboxy-2methylpropyl)- and S-(2-carboxyethyl)-L-cysteine by man was followed by the excretion in the urine of the unchanged amino acid and the N-acetylated compounds. 2. In the rat the fraction of S-(2-carboxy-1-methylethyl)-L-[U-14C]cysteine acetylated increased as the dose level decreased. 3. The significance of these results for the excretion of S-carboxyalkyl-cysteines in man is discussed.

The localization and some properties of the N-deacetylase of Ascaris lumbricoides var suum.

1. Hydrolysis of acetanilide by the nematode Ascaris lumbricoides var suum occurred in the cytosol of the intestinal epithelium and to a lesser degree in the cytosol of the reproductive organs. Cuticle and mesenchyme fluid showed no measurable activity. 2. The molecular weight of the enzyme responsible for hydrolysis was estimated to be about 90 000. 3. Hydrolysis of N-acetyl compounds occurred optimally at pH 7-4 at 30-35 degrees and at a substrate concentration of 10(-2) M. 4. The reaction was inhibited 50% by Cu2+, Zn2+, n-ethylmaleimide or p-chloromercuribenzoate at 10(-4) M. The anthelmintic organophosphates inhibited N-deacetylation by 50% at 10(-7) M. Dithiothreitol enhanced the reaction rate but glutathione and thioglycollic acid were without effect.

Biopharmaceutical study of the hepato-biliary transport of drugs. V. Hepatic uptake and biliary excretion of organic cations.

The hepato-biliary transport characteristics in vivo and the uptake process by liver slices and by liver cell suspensions were studied in rats using procaineamide ethobromide, its N-acetyl compound and quinine. These organic cations were transported from plasma to liver and from plasma to bile against a concentration gradient, and their biliary excretion was depressed by an administration of the other organic cations in accordance with earlier studies. However the hepatic uptake of quinine was extremely high, 39 of the liver/plasma concentration ratio, as compared with 8.6 of PAEB and 1.7 of APAEB. When taken up by liver slices or liver cell suspensions, PAEB and quinine showed completely different patterns. Slice/medium ratio of PAEB obtained by liver slices attained 3.6 after 4 hours and cell/medium ratio obtained by liver cell suspensions did not attain one. On the other hand, slice/medium and cell/medium ratios of quinine attained about 20 and the high slice/medium ratio was only slightly decreased in an atmosphere of nitrogen or in the presence of DNP. The hepatic high uptake of quinine observed both in vivo and in vitro is mostly explainable by lipid-binding mechanism as the binding to liver lipids showed quite a high value, 77%.

On the chemical reactivity of aminoacyl-tRNA ester bond: I - Influence of pH and nature of the acyl group on the rate of hydrolysis

Summary We have studied the base catalyzed hydrolysis of valyl-tRNA and N-acetyl-valyl tRNA as a function of pH, at 37°C and I = 0.3. The fully protonated form is found to hydrolyse 90 times faster than the unprotonated one (second order rate constant: 2.30.104 1.M−1min−1 compared to 2.50.102 1.M−1min−1). For the N-acetylated compound the rate constant is 4.16.102 1.M−1min−1. The pKa of the valyl-tRNA amine function is found to be 7.5. The variation of rate constants as a function of the acyl part shows that the base catalyzed hydrolysis of acyl-tRNAs is very sensitive to the inductive effect of the acyl moiety. The lability of the aminoacyl-tRNA ester bond is discussed.

Acyl Alkyl Diimides. III. Influence of Structure on Decomposition

Eleven compounds of general structure RCON=NC(CN)R2′, where R = C6H5, CH3, C6H5CH2, and R2′ = (CH3)2, (CH2)4, (CH2)5, (CH2)6, have been found to decompose in a first-order manner in dilute toluene solution in the temperature range 60–100°. The N-acetyl compounds decompose ca. four times faster than the corresponding N-benzoyl cases. Variation in R2′ causes changes in rate parallel to those observed by Overberger for the analogous bis-α-cyanoalkyl diimides but of smaller magnitude. The products are those expected from homolytic cleavage, and intermediate N-acylketenimines have been trapped by added water in two cases.

黒麹菌によるパラアミノサリチル酸誘導体のN-アセチル化

In the course of study on the microbial transformation of p-aminosalicylic acid derivatives, Black Aspergilli (Asp. awamori 5002 and Asp. aureus 5494) was found to produce metabolic products. These metabolites have been isolated, purified and identified as N-acetylated compounds by comparison with the synthetic compounds by thin-layer chromatography, infrared spectrophotometry and nuclear magnetic resonance spectroscopy.

Studies of the Synthesis of Furan Compounds. XXVII. Derivatives of 3-(5-Nitro-2-furyl)acrylonitrile

Abstract In a continuation of our previous papers concerning the syntheses with 5-nitro-2-furonitrile, 2-(5-nitro-2-furyl)vinyl-1,2,4-oxadiazoles and -1,2,3-triazoles were prepared from 3-(5-nitro-2-furyl)acrylonitrile (I). When I was treated with diazomethane in ether, 4-[2-(5-nitro-2-furyl)vinyl]-1,2,3-triazole (II) was obtained. II gave N-acetyl (IIa) and N-morpholinomethyl (IIb) compounds when treated with acetic anhydride and when the Mannich reaction was utilized respectively. 3-(5-Nitro-2-furyl)acrylamide oxime (III) was prepared by the usual method from I and hydroxylamine. The treatment of III with benzaldehyde and acid anhydrides or chlorides afforded 3-[2-(5-nitro-2-furyl)vinyl]-5-phenyl-4,5-dihydro-1,2,4-oxadiazoline (IV) and O-acyl-3-(5-nitro-2-furyl)acrylamide oximes (IIIa—IIIe) respectively. The O-acyl-amide oximes were found to cyclize to 3-[2-(5-nitro-2-furyl)vinyl]-5-alkyl-1,2,4-oxadiazole (V–VII) in their thermal analyses.

Reaction of Biguanides and Related Compounds. V. The Base-catalyzed Condensation of Benzil with 1, 1-Dialkylguanidine

1, 1-Dialkylguanidine reacted with benzil in the presence of sodium ethoxide to give 2-dialkylamino-4-oxo-5, 5-diphenylimidazoline, from which N-acetyl compound was successfully obtained by heating with an great excess of acetic anhydride. The structures of these compounds were confirmed by mass spectra and infrared spectra.

Azabenzocycloheptenones. Part XV. Synthesis of benzazatropones and a quinoline aldehyde by the dehydrogenation of certain tetrahydro-1-benzazepine derivatives

4,4,7,9-Tetrabromo-1,2,3,4-tetrahydro-1-benzazepin-5-one (IV) reacts with lithium chloride in dimethylformamide to give 6,8-dibromoquinoline-4-carbaldehyde (VII) and with active manganese dioxide to give 4,7,9-tribromo-1-benzazepin-5-one (I; R1= R4= H, R2= R3= R5= Br) and 4,7,9-tribromo-1-benzazepine-2,5-dione (VI; R1= Br, R2= H). The latter has been converted into 4,7,9-tribromo-2-chloro-1-benzazepin-5-one (I; R1= Cl, R4= H, R2= R3= R5= Br). 1,2,3,4-Tetrahydro-2-methyl-1-p-tolylsulphonyl-1-benzazepin-5-one (XIII; R = tosyl), the N-acetyl derivative (XIII; R = Ac) and several related compounds are reported. Treatment of ethyl γ-[N-(o-methoxycarbonylphenyl)acetamido]butyrate (XVI; R1= Ac, R2= H) with potassium t-butoxide gave ethyl γ-(1,2-dihydro-4-hydroxy-2-oxoquinolin-1-yl)butyrate (XVII).

Studies on Mesoionic Compounds. II. Synthesis of N-Acyl Derivatives of 3-Dialkylaminosydnonimines

A number of N-acyl and N-nitroso-3-dialkylaminosydnonimines (II) were synthesized by various acylating methods. In some cases, the acylation with activated esters, mixed anhydrides or dicyclohexylcarbodiimide was found to be more favorable. The reactivities of these derivatives towards acids and alkalis were investigated. Trifluoroacetyl (II-6) and formyl (II-1) compounds were easily deacylated in varuous conditions. Methylation took place at the acylated imino nitrogen of N-ethoxycarbonyl compound to give the quaternary salt (II-18). N-Acetyl compound (II-2) was compared with its 3-alkyl analog in the physicochemical properties ; its pKa values reveals that the morpholino group has little effect on the basicity of the compound.

Synthesis and Cytotoxicity Study of Some Acetylisatins and Diazobiphenyls

Nitrogenous heterocyclic compounds, oxindoles especially isatins and related heterocyles have excellent antifungal, anti-inflammatory, antimicrobial and anticancer activities. Oxindoles keto lactams (1-3) were synthesized according to modified Sandmayer method and their N-acetylated compounds (4-6) gave diazo-biphenyls (7-10) through ring cleavage and consequent cyclization reaction. Bis-amide (11), and Schiff-base (12) were synthesized from oxindoles respectively. The investigation of cytotoxicity of the synthesized compounds was carried out against brine shrimp lethality bioassay. In our present investigation some of the synthesized compounds such as halogen substituted acetylisatins (4-6) and the ring extended diazo-biphenyls, (7-10) have been shown to exhibit strong cytotoxic effect. Key words: diazo-biphenyls; oxindoles; cytotoxicity; brine shrimp DOI: 10.3329/dujps.v9i1.7423Dhaka Univ. J. Pharm. Sci. 9(1): 1-6, 2010 (June)

The enzymatic degradation of heparitin sulfate. II. Isolation and characterization of non-sulfated oligosaccharides.

Abstract A non-sulfated, N-acetylated disaccharide was isolated from hepatirin sulfate after enzymatic digestion. This compound containing α, β unsaturated uronic acid is an isomer of a disaccharide obtained previously from hyaluronic acid. It contains an α- d -(1 → 4) rather than the β- d -(1 → 3) linkage found in the hyaluronate compound. The isolation of another non-sulfated, N-acetylated compound, most likely a tetrasaccharide, indicates that at least two or more N-acetylated units occur in sequence in the polysaccharide. The linkages in the non-sulfated portion of heparitin sulfate appear to be mainly α- d -(1 → 4) .

Degradations of allosecurinine.

Degradations of allosecurinine (III) gave the N-acetyl amino-lactone (IX), lactam-car-binol C (XIII), quinolizidine C (XVI), tetrahydroallosecurinine (XVIII) and compound (XIX). Identifications of the former three compounds (IX), (XIII) and (XVI) with the corresponding synthetic specimens provided a definite proof for the relative configuration of allose-curinine (III).

STUDIES ON THE ALKALOIDS OF MENISPERMACEOUS PLANTS. CCI. STRUCTURE OF TRILOBINE AND ISOTRILOBINE. (16). STRUCTURE OF TRILOBINE

The structure of trilobine was reported by Inubushi and Nomura as the formula (I) from the cleavage reaction of its N-acetyl compound with metallic sodium in liquid ammonia. The antipodal isotrilobine (II) was synthesized from dlhydroepistephanine (V) by the present writers.In the present series of work, O-methylanhydrodemethyl-N-ethyl-dihydroepistephanine (X) was synthesized from N-ethyldihydroepistephanine (VII) by a similar method. X came as a picrate of m.p. 194-195°, [α]D-283.1° (acetone), C37H38O5N2⋅2C6H3O7N3⋅1 1/2H2O. By comparison with the picrate, m.p. 193-195°, [α]D+283.8° (acetone), C37H38O5N2⋅2C6H3O7N3⋅1 1/2H2O, of the N-ethyl compound (III) from natural trilobine (I), X was found to be its antipode (cf. Table I). Consequently, the structure of trilobine was reaffirmed as I by synthesis.

2-Amino sugar-containing oligosaccharides isolated from hydrazinolyzate of blood group A mucopolysaccharide of hog gastric mucus. II. Isolation and characterization of O-beta-2-acetamido-2-deoxy-D-glucopyranosyl-(1-6)-D-galactose and O-beta-2-acetamido-2-deoxy-D-glucopyranosyl-(1-3)-[O-beta-2-acetamido-2-deoxy -D-glucopyranosyl-(1-6)]-D-galactose.

The large fractions 4 and 5, described in the first report, obtained after the first cellulose powder column chromatography of the N-acetylated 2-amino sugar-containing compounds which were separated from the acid hydrolyzate of the hydrazinolyzed product of blood group A mucopolysaccharide of hog gastric mucus, were further fraction ated on cellulose powder columns and char coal columns. Of the fractions, a disaccharide (Oligo saccharide III) and a trisaccharide (Oligosac charide IV) were isolated. On the basis of the analytical data as well as the values of sodium metaperiodate oxidation before and after reduction with sdyodium borohydride and their physical properties, the structures of these compounds have been firmly established: Oligosaccharide III is O-β-2-acetamido-2-deoxy-D-glucopyranosyl-(1→6)-D-galactose and Oligosaccharide IV is O-β-2-acetamido-2-dexoy-D-glucopyransol-(1→3)-[O-β-2acetamido-2-deoxy-D- glucopyra-(1→6)-]-D-galactose.

Heats of Aminolysis and Hydrolysis of Some N-Acetyl Compounds and of Acetic Anhydride.

Heats of Aminolysis and Hydrolysis of Some N-Acetyl Compounds and of Acetic Anhydride.

Electrolytic Reaction of ω-Amino Compounds and Their Acyl Derivatives. IV. The Electrolytic Preparation of the ω-Amino Acids by the Acidic Electrochemical Oxidation of Their Corresponding N-Acetylpolymethylenediamines. (Comparative Studies on the Acidic Electrochemical Oxidation of Simple Diaminoalkanes with Their N-Acetyl Compounds)

Electrolytic Reaction of ω-Amino Compounds and Their Acyl Derivatives. IV. The Electrolytic Preparation of the ω-Amino Acids by the Acidic Electrochemical Oxidation of Their Corresponding N-Acetylpolymethylenediamines. (Comparative Studies on the Acidic Electrochemical Oxidation of Simple Diaminoalkanes with Their N-Acetyl Compounds)

A micromethod for the colorimetric determination of N-acetyl groups in acid mucopolysaccharides

Deacetylation of mucopolysaccharides and other N-acetylated compounds with 2 N HCl-methanol is a useful and simple procedure for determining N-acetyl groups in these compounds. The acetyl groups are converted to methyl acetate which is colorimetrically determined as a hydroxamic-ferric complex. This method permits the determination of N-acetyl groups in a range of 1 to 10 μmoles and is more sensitive than previously described methods. The reproducibility and some of the factors affecting the deacetylation and colorimetric analysis have been studied.

フラン誘導体の合成研究 (第16報)

1) 1-(2-Furyl)-1-methoxy-2-nitroethane (II) was prepared in a good yield By condensation of furfural with nitromethane, in the presence of a small amount of sodium methoxide.2) The amount of 1-(2-furyl)-2-nitroethylene (I) to (II) in the condensation mixture was calculated from the elaborated chart of the refractive index of the above two components.3) After reducing (II) with zinc dust in 5% acetic solution, the amino componud was acetylated with acetic anhydride. Nitration of the N-acetylated compound (IV) with a mixture of acetic anhydride and conc. nitric acid was accomplished.4) 2-Amino-3-(2-furyl)-3-methoxypropanol (IX) was prepared in a stepwise manner from (II) by hydroxymethylation and reduction. N-[1-Acetoxymethyl-2-(2-furyl)-2-methoxyethyl]-dichloroacetamide (XI) was synthesized from (IX) by acylation of the amino group with dichloroacetic acid and then of hydroxyl group with acetic anhydride in the presence of a small amount of pyridine. Nitration of the above two acylated compounds failed to give the desired crystalline product.

アルカミン類の研究 (第2報)

It was assumed that the monochloro compound (I), m.p. 193-194°, obtained from dl-threo- and dl-erythro-1-phenyl-2-aminopropane-1, 3-diol hydrochloride is the threo compound. Acetylation (II) of this monochloro compound, followed by saponification (III→IV), yielded an N-acetyl erythro compound (V). The mechanism of this reaction was assumed to be one example of a participation of acyl group in replacement reaction, probably via oxozalidinium compound (III). By the reactions described in the Reports I and II, it has become possible for a reciprocal inversion to occur between an erythro and a threo compound, as shown in the accompanying Tables.