4-Acetaminophenoxyacetic acid,a new urinary metabolite of phenacetin

Summary It is shown that 4-acetaminophenoxyacetic acid (APOA) is an urinary metabolite of phenacetin. APOA was isolated by means of silica gel TLC in various solvent systems from the urine of rats, dogs, and humans, collected 24 h after p.o. treatment with phenacetin (rats and dogs: 200 mg/kg; humans: three single doses of 0.5 g). Expressed as a percentage of the dose, APOA was detected at levels of 1% in rats, 0.13% in dogs and 0.04% in humans. 4-Acetaminophenoxyacetic acid was identified as its methylester—synthetized in the reaction of APOA and diazomethene—by thin layer chromatography, UV absorbance, melting point, and mass spectroscopy.     

2-Mercapto-1-methyl-5-methylmercapto-imidazole: a new metabolite of thiamazole

1. 2-Mercapto-1-methyl-5-methylmercapto-imidazole (13) was found in urine samples of man and rat after intake of thiamazole (1).

2. It is assumed that the metabolite is produced via a N-oxidation intermediate enabling a nucleophilic attack at carbon-5 in the thiazole ring.     

Isolation and characterization of 4'-hydroxy T-2 toxin, a new metabolite of the trichothecene mycotoxin T-2

Biotransformation of the trichothecene mycotoxin T-2 by the hepatic S-9 fraction prepared from phenobarbital-treated rats yielded a new metabolic product designated RLM-3. The metabolite was purified from the hepatic preparation using preparative HPLC. The structural analysis of RLM-3 was carried out using gas chromatography/mass spectrometry and 1H and 13C NMR. RLM-3 was identified as 4'-hydroxy T-2. The toxicity of RLM-3 in comparison to T-2 toxin and 3'-hydroxy T-2 was assessed using a rat skin bioassay technique. The metabolite 4'-hydroxy T-2 was shown to be deacylated at the C-4 position to yield 4'-hydroxy HT-2 when incubated with rat hepatic S-9 preparations.     

N-hydroxyphenacetin, a new urinary metabolite of phenacetin in the rat

N-Hydroxyphenacetin has been found in the urine of rats dosed with phenacetin, extending previous reports that phenacetin is N-hydroxylated by liver microsomes in vitro. After an oral dose of phenacetin (500 mg/kg) urine was collected for 24 hr, conjugates hydrolyzed with extract of Helix pomatia, and the metabolites extracted with dichloromethane and treated with diazomethane. Methylation of N-hydroxyphenacetin produced a stable derivative, N-methoxyphenacetin, which was separated from most other metabolites by thin layer chromatography. Identification of N-methoxyphenacetin was by combined gas chromatography-mass spectrometry and comparison with the synthetic reference compound. Quantification by gas chromatography with flame-ionization detection showed that 0.023% of the dose phenacetin was recovered from urine as N-hydroxyphenacetin. It is probable that this value considerably underestimates the extent of phenacetin N-hydroxylation in vivo, inasmuch as N-hydroxyphenacetin is known to be rapidly degraded in biological systems.     

珊瑚菌菌体培养物的新天然产物 （英文稿）

目的 对珊瑚菌(Clavicorona pyxidata)菌体培养物的活性成分进行分离。方法 用多种色谱技术对化合物进行分离纯化,并用光谱技术和单晶X射线衍射技术鉴定化合物的结构。结果 从中分离到2个化合物: clavicoronol(1)、腺苷(2)。结论 化合物1为新化合物,并通过单晶X射线衍射技术确定了2的立体构型。