N-(4-氯-3-甲基苯基)-N′-甲基脲的合成

用铁粉还原、水汽蒸馏的方法制得4－氯－3－甲基苯胺，再以1，2，4－三氯苯为溶剂，与N－甲基脲直接缩合合成N－（4－氯－3－甲基苯基）－N′-甲基脲，该新方法优化了反应条件，可获得60％及67％的转化率和收率，且未反应的原料可回收套用。     

2，5—二甲氧基—4—丙硫基—β—硝基苯乙烯的合成方法改进

报道了2，5－二甲氧基－4－丙硫基－β－硝基苯乙烯的合成，以2，5－二甲氧基苯甲醛为起始原料，经溴代、丙硫醇取代及与硝基甲烷缩合反应，合成了2，5－二甲氧基－4－丙硫基－β－硝基苯乙烯。     

3-氯-2,4,5-三氟苯甲酸的合成

目的：合成3－氯－2，4，5－三氟苯甲酸。方法：以3，4，5，6－四氟苯二甲酸为起始原料，经酯化、氨化、重氮化和桑德迈耳反应制得3－氯－2，4，5－三氟苯甲酸。结果；酯化时使用发烟硫酸；重氮化和桑德迈耳反应时溶剂由水改为水和二氯乙烷，使产率增加，质量提高。结论：该合成路线条件温和、操作简单，收率提高到61．8％。     

氟罗沙星的合成

以6，7，8－三氟－1，4－二氢－4－氧代－3－喹啉酸乙酯为原料，经氟乙基化、与N－甲基哌嗪缩合和水解等3步反应制得氟罗沙星，总收率67．5％。工艺操作简单，适于工业生产。     

3-吡啶乙酸盐酸盐的合成

以烟酸乙酯为原料，经还原、氯代、氰化、水解等反应合成了骨吸收抑制剂利塞膦酸钠中间体3－吡啶乙酸盐酸盐。原料易得，反应条件温和，操作方便，总收率28．4％。     

3β-羟基孕甾-5-烯-20-酮-3-醋酸酯的合成工艺改进

双烯醇酮醋酸酯在活性镍催化氢化反应后得到的副产物3β，20（R，S）－二羟基孕甾－5－烯－3－醋酸酯通过适当的氧化反应可制成3β－羟基孕甾－5－烯－20－酮－3－3醋酸酯，后者可用于黄体酮生产。     

4-苯基-5-乙氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮的绿色合成研究

目的探索操作简便,环境友好的4－苯基－5－乙氧羰基－6－甲基－3,4－二氢嘧啶－2（1H）－酮的合成方法。方法 以苯甲醛、乙酰乙酸乙酯和尿素作为起始原料,在无溶剂和微波加热条件下,选择1－丁基－3－甲基咪唑氯盐和1－丁基－3－甲基咪唑－L－乳酸盐两种不同的离子液体分别催化Biginelli反应制备4－苯基－5－乙氧羰基－6－甲基－3,4－二氢嘧啶－2（1H）－酮,并比较两种离子液体的催化效果。结果两种离子液体在微波、无溶剂条件下均可催化Biginelli反应制得目标化合物,其中1－丁基－3－甲基咪唑－L－乳酸盐作为催化剂目标化合物收率较高。结论以离子液体－丁基－3－甲基眯唑－L－乳酸盐作为催化剂,经微波、无溶剂Biginelli反应制备4－苯基－5－乙氧羰基－6-甲基－3,4－二氢嘧啶－2（1H）－酮,是一种易于操作的绿色合成方法。     

1,1-二苯基丙酮合成工艺改进

以硫酰氯对苯基丙酮进行氯代反应得到1－氯苯基丙酮，无需分离即可直接与苯进行Friedel-Crafts反应得到1，1－二苯基丙酮。总收率71％，较现行溴代工艺成本可下降30％。     

4-氨基-7-硝基苯并[1,2,5]噁二唑的合成

以2，6－二氯苯胺为原料，通过氧化环化、硝化、叠氮化、氨化等5步反应，得到4－氨基－7－硝基苯并[1,2,5]恶二唑，并对反应条件、精制方法进行了改进。总收率20．1％。     

萘普生中间体2-氨基-2-(5-溴-6-甲氧基-2-萘基)丙酸的合成

采用1，3－二溴－5，5－二甲基乙丙酰脲作催化剂，在丙酮溶剂中，以盐酸作催化剂，于室温快速(8min)、高收率（96％）地对2－甲氧基萘的萘环进行溴化，再经乙酰化、Bucherer-Berg环化和水解反应，制得萘普生中间体2－氨基－2－（5－溴－6-甲氧基－2－萘基）丙酸。并对环化反应的条件进行了优化，反应总收率68％。     

Metabolic fate of gallic acid orally administered to rats

The metabolic behavior of orally administered gallic acid was investigated by HPLC and 4-O-methyl gallic acid was found to be the main metabolite in rat peripheral blood and urine. After oral administration of gallic acid, maximum concentration in portal vein and inferior vena cava occurred at 15 and 30 min, respectively. In portal vein, gallic acid was preferentially detected relative to 4-O-methyl gallic acid, whereas gallic acid and 4-0-methyl gallic acid were equally detected in inferior vena cava. On the other hand, 4-O-methyl gallic acid but not gallic acid was found in liver. The contents of gallic acid and 4-O-methyl gallic acid in urine were nearly 100 times higher than those in blood. The ratio of 4-O-methyl gallic acid to total gallic acid metabolites in urine was from 0.55 to 0.76, indicating that a considerable amount of gallic acid was excreted without being metabolized. In this study we found that gallic acid administered orally existed in the blood for 6 h at most, and more than half was metabolized to 4-O-methyl gallic acid, followed by excretion into urine.     

A comparison of effects of sulfasalazine and its metabolites on the metabolism of endogenous vs. exogenous arachidonic acid

Sulfasalazine and, to a lesser extent, 5-aminosalicylic acid and N-acetyl-aminosalicylic acid, were found to block production of 5-hydroxy-6,8,11,14-eicosatetraenoic acid, leukotriene B4 (LTB4), and LTB4 stereoisomers from both exogenous and endogenous [14C]arachidonic acid (14C-AA) in ionophore A23187 (1 microgram/ml)-stimulated human neutrophils. Lipids were assessed by thin-layer chromatography and reverse-phase high-pressure lipid chromatography. Sulfasalazine blocked the synthesis of these metabolites from both exogenous and endogenous AA, but was more effective in blocking the metabolism of exogenous than endogenous AA. The IC50 for sulfasalazine in blocking the synthesis of LTB4 was 0.8 mM when exogenous AA was the substrate and 2.8 mM when endogenous AA was the substrate. N-Acetyl-aminosalicylic acid showed a similar pattern, but was less effective than sulfasalazine (IC50 for exogenous AA was 5.4 mM, and for endogenous AA was 8.0 mM). 5-Aminosalicylic acid had similar effects with an IC50 of 6.0 and 6.4 mM respectively. Sulfasalazine but not 5-aminosalicylic acid inhibited the incorporation of arachidonic acid into phospholipids and triglycerides. Sulfasalazine, but not its metabolites, inhibited the release of 14C-AA from membrane phospholipids in a dose-dependent manner (46.0% inhibition with 4 mM sulfasalazine). Sulfasalazine also blocked the metabolism of exogenously added LTB4 to 20-OH LTB4 and 20-COOH LTB4 with an IC50 of 2 mM. Our findings suggest that under physiologic conditions, with endogenous AA as a substrate, sulfasalazine acts as an inhibitor of lipoxygenase, of phospholipase A2 and of LTB4 metabolism, whereas 5-aminosalicylic acid and N-acetyl-aminosalicylic acid inhibit only lipoxygenase.     

Convenient synthesis of (RS)-4-amino-3-hydroxybutyric acid

A new three-step synthesis of 4-amino-3-hydroxybutyric acid from an inexpensive starting material and under mild reaction conditions is described. Crotonic acid was brominated by the Wohl-Ziegler reaction to 4-bromocrotonic acid, which, in turn, was converted with ammonium hydroxide into 4-aminocrotonic acid. This compound, refluxed in water in the presence of a strong acid resin, afforded 4 amino-3-hydroxybutyric acid in good yields.     

The Metabolism of Mebeverine in Man: Identification of Urinary Metabolites by Gas Chromatography/Mass Spectrometry

The urinary metabolites of orally administered mebeverine hydrochloride (270 mg) were studied in five healthy volunteers with the aid of gas chromatography/mass spectrometry. Mebeverine, which is an ester of veratric acid and 4-{ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino}butan-1-ol, was completely hydrolysed to the corresponding acid and alcohol moieties. The acid moiety was subsequently O-demethylated to vanillic acid and isovanillic acid, which in turn were further O-demethylated to protocatechuic acid. The alcohol moiety was O-demethylated to the corresponding phenol 4-{ethyl-[2-(4-hydroxyphenyl)-1-methylethyl]amino}butan-1-ol. In 24 hr, 44% of the dose was accounted for as follows: Veratric acid 32%, vanillic acid 2.7%, isovanillic acid 6.5%, 4-{ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino}butan-1-ol 0.9% and 4-{ethyl-[2-(4-hydroxyphenyl)-1-methylethyl]amino}butan-1-ol 2.1%. Only trace amounts of protocatechuic acid were found in the urine. The results indicated that the metabolites were mostly excreted as conjugates. The total excretion of the acid moiety, unchanged or in the form of metabolites was 97.6%. The corresponding value for the alcohol moiety was 5.5%.     

A comparison of the effects on blood glucose and ketone-body levels, and of the toxicities, of pent-4-enoic acid and four simple fatty acids

Some effects of the hypoglycaemic compound pent-4-enoic acid in rats and mice, are described. Pent-2-enoic acid, pentanoic acid, cyclopropanecarboxylic acid and cyclobutanecarboxylic acid, which were shown to be non-hypoglycaemic, were used as controls. Pent-4-enoic acid and cyclopropanecarboxylic acid caused ketosis in rats, with a lowering of the blood β-hydroxybutyrate/acetocetate (βHB/AcAc) ratio; some ketosis was caused by the other fatty acids but the βHB/AcAc ratio was not changed. Pent-4-enoic acid caused an increase in free fatty acid concentration in rat plasma. The acute toxicities of these compounds in mice were determined. The mechanism of the hypoglycaemic action of pent-4-enoic acid is discussed in relation to that of hypoglycin.     

Influence of the gut microflora on the metabolism of 4-nitrobenzoic acid in the marmoset

1. 4-Nitrobenzoic acid was metabolized by the marmoset to amino derivatives to the extent of 18.8% (p.o.) and 11.4% (i.p.) of the dose.

2. Reduction of 4-nitrobenzoic acid was significantly decreased by antibiotic pretreat-ment; the mean decrease in reduction was 81% for animals dosed orally and 73% for intraperitoneally dosed marmosets.

3. 4-Nitrohippuric acid was the major metabolite of 4-nitrobenzoic acid, accounting for 30.6% and 49.6% of p.o. and i.p. doses respectively.

4. Antibiotic pretreatment affected the marmosets″ normal capacity to reduce 4-nitrobenzoic acid for many weeks after the initial administration.

5. Maximum radioactivity in the blood, after an oral dose, was reached in 30-40min; the average half-life for the elimination of 4-nitro[carboxy-¹⁴C]benzoic acid and its metabolites was 30.4±3?min after an intramuscular dose.

6. Radioactivity of 4-nitro[carboxy-¹⁴C]benzoic acid representing 3.4% of the dose was excreted in rat bile in 24h.     

The effect of ascorbic acid on the conjugation of 4-hydroxybiphenyl in rat isolated hepatocytes

Ascorbic acid at high non-physiological levels inhibited the sulphation of 4-hydroxybiphenyl by rat isolated hepatocytes. Glucuronylation of 4-hydroxybiphenyl, formed from 4-methoxybiphenyl, was increased at ascorbic acid levels which inhibited sulphation. The glucuronylation of 4-hydroxybiphenyl added directly to the cells was enhanced at concentrations of ascorbic acid which did not inhibit sulphation. Ascorbic acid did not influence the cytochrome P-450-dependent O-demethylation of 4-methoxybiphenyl or the level of cellular lipid peroxidation.     

Diphenyl ether cleavage of 3-phenoxybenzoic acid by chicken kidney microsomal preparations.

Incubation of 3-phenoxybenzoic acid[carbonyl-14C] with chicken kidney microsomal fraction produced two major radioactive compounds identified as 3-hydroxybenzoic acid and 4'-hydroxy-3-phenoxybenzoic acid. It was found that 4'-hydroxy-3-phenoxybenzoic acid was transitory in nature and was rapidly converted into 3-hydroxybenzoic acid. The conversion of 3-phenoxybenzoic acid to the products was NADPH dependent. This is a first example of metabolism of 4'-hydroxy-3-phenoxybenzoic acid to 3-hydroxybenzoic acid. Cytosol did not promote any cleavage. Similar activities were present in liver microsomes, but the activity was lower than in kidney. Intestinal contents, homogenates, or microsomal fractions did not metabolize 3-phenoxybenzoic acid.     

Phenolic components and antioxidant activity of Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos

Fernblock, an aqueous extract of the aerial parts of the fern Polypodium leucotomos, used as raw material for topical and oral photoprotective formulations, was fractioned by HPLC and the main components with antioxidant capability were identified by means of UV spectra, electrochemical detection, and MSn. Phenolic compounds were identified as 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, vanillic acid, caffeic acid, 4-hydroxycinnamic acid, 4-hydroxycinnamoyl-quinic acid, ferulic acid, and five chlorogenic acid isomers. Total ferric antioxidant capacity (FRAP) of HPLC eluted fractions was measured. The results suggest that the herein identified compounds support, at least partially, the antioxidant and radical scavenging capacities of Fernblock.     

Identification of 4-oxo-13-cis-retinoic acid as the major metabolite of 13-cis-retinoic acid in human blood

The metabolites of 13-cis-retinoic acid (Accutane) were investigated in blood samples from human volunteers on chronic treatment for dermatological disorders. The major metabolite was isolated by reverse-phase high-pressure liquid chromatography and identified as 4-oxo-13-cis-retinoic acid by comparison of its mass and NMR spectra to the spectra of the reference compound. 4-Oxo-all-trans-retinoic acid was also identified, but the extent to which this compound was a metabolite of 13-cis-retinoic acid or an artifactual isomerization product of the major metabolite is unknown. Chromatographic data suggested that small amounts of 13-cis-retinoic acid, 4-hydroxy-13-cis-retinoic acid, and dioxygenated metabolites of 13-cis-retinoic acid may also be present in the blood. This study indicates that a major metabolic pathway of 13-cis-retinoic acid in humans is oxidation at C4 of the cyclohexenyl group.