用2H-标记物和GC-MS分离鉴定联苯双酯在大鼠尿中的一个代谢产物

Dimethyl-4, 4′-dimethoxy-5, 6, 5′, 6′-dimethylenedioxybiphenyl-2, 2′-dicarboxylate (biphenyldimethyldicarboxylate; BDD), a synthetic compound, has been used in the treatment of chronic hepatitis with good results in reducing s-GPT. Previous work in our laboratory studied its metabolites using ³H-labeled compound in combination with TLC and found that its main methabolic pathway is demethylation followed by conjugation with glucuronic acid. This paper reports the isolation and identification of a metabolite of BDD from rat urine using ²H-labeled compound and GC-MS. Rats fasted for 12h were intragastrically given a mixture of ²H-labeled (consisting of monodeutero-and dideutero-BDD in the ratio about 1:1.3)and non-labeled BDD 150mg/kg and placed in metabolism cages for urine collection. The 24h urine was filtered and extracted three times each with 5ml of methylenedichloride. The extracts were pooled and evaporated to dryness under reduced pressure at 35℃. The residue was redissolved in chloroform and subjected to GC-MS analysis. The mass spectrum (m/z: 404, 405, 406; 373, 374, 375; 345, 346, 347; 330, 331, 332; etc)indicates that the molecular ionic and fragment peaks of the metabolite all have 14 amu less than those of BDD. This means that the metabolite isolated is mono-O-demethylated BDD. The result confirmed our findings reported previously.     

抗肿瘤药物的研究:N′,N″-二螺三哌嗪类化合物的合成

In order to search for new antitumor drugs, sixteen N′, N″-dispirotripiperazine derivatives were synthesized from N′, N″-dispirotripiperazinium dichloride dihydrochloride by substitution, acylation and Mannich reaction. Six compounds were selected for preliminary pharmacological test. The result showed that five compounds possess inhibitory action against carcinoma S₃₇ in rats. The inhibitory activity of compounds Ⅵ and Ⅹ was 55.0% and. 41.9% respectively.     

铀促排药物研究——Ⅲ.2,3-二羟基-5-烷氧羰基苄基胺羧酰胺螯合剂的合成

In searching for new chelation therapy drugs against uranium intoxication, a series of N-carboxymethyl-N-(substituted carbamoylmethyl)-2, 3-dihydroxy-5-carboalkyloxybenzylamine was synthesized starting with 2, 3-dihydroxy-5-carboalkyloxybenzylamine diacetic acid. The effect on the elimination of uranium salts from animal bodies was tested. Four of them (Ⅳ_n, Ⅳ_q, Ⅳ_u and Ⅳ_v) were shown to be more effective than tiron or phosphicine in accelerating uranium excretion in rats.     

甘草叶中甘草宁P-3′-甲醚的分离和鉴定

Two flavonoids were isolated from the leaves of Glycyrrhiza uralensis Fisch (Licorice, Leguminosae). On the basis of physico-chemical properties and spectroscopy (UV, ¹HNMR and MS), a new compound was elucidated as 3,5,7,4′-tetrahydroxy-3′-methoxy- 6-isoprenyl flavone (gancaonin P-3′-methylether) and another known compound was identified as 8-C-prenyleriodictyol.     

上海地区人群甲型H1N1流感抗体水平监测分析

Objective To understand levels of antibody to swine-origin influenza A(H1 N1) virus (A/ H1N1) among different age groups in Shanghai, and to compare the levels between antibodies to A/H1N1 and to 2008-2009 seasonal influenza vaccine virus A/Brisbane/59/2007(H1N1). Methods The anti-A/HlN1 antibody levels were determined among 5 age groups (0-5 months, 6 months-4 years, 5-24 years, 25-59 years, and ≥60 years) with routine micro-hemagglutination inhibition test. The positive rates of the antibodies among different age groups were compared by Pearson's X2 test and Fisher' s exact probability test. Results The positive rate of antibody to A/H1N1 in the whole population in Shanghai was 9.2% (37/404). The highest rate was 25.0% (21/84) in the age group of ≥60 years, the next was 10. 0% (8/80) in the age group of 25-59 years, the positive rates in other groups were lower. The result of Pearson's X2 test showed that there were statistically significant differences in the positive rates of the antibodies among different age groups. Of 329 sera positive for antibody to 2008 -2009 seasonal influenza vaccine virus A/Brisbane/59/ 2007 (H1N1), 31 had anti-A/HlNl antibodies, and of 75 sera negative for antibody to A/Brisbane/59/ 2007(H1N1), 6 had anti-A/HlNl antibodies. The result of Pearson's X2 test showed that there were no significant differences in positive rates of antibody to A/H1N1 between the two types of population. Conclusions The anti-A/HlNl levels in Shanghai population are low, and people are generally susceptible to A/H1N1. The sera positive for antibody to A/Brisbane/59/2007(H1N1) can not provide cross-protection against A/H1N1.     

上海地区人群甲型H1N1流感抗体水平监测分析

Objective To understand levels of antibody to swine-origin influenza A(H1 N1) virus (A/ H1N1) among different age groups in Shanghai, and to compare the levels between antibodies to A/H1N1 and to 2008-2009 seasonal influenza vaccine virus A/Brisbane/59/2007(H1N1). Methods The anti-A/HlN1 antibody levels were determined among 5 age groups (0-5 months, 6 months-4 years, 5-24 years, 25-59 years, and ≥60 years) with routine micro-hemagglutination inhibition test. The positive rates of the antibodies among different age groups were compared by Pearson's X2 test and Fisher' s exact probability test. Results The positive rate of antibody to A/H1N1 in the whole population in Shanghai was 9.2% (37/404). The highest rate was 25.0% (21/84) in the age group of ≥60 years, the next was 10. 0% (8/80) in the age group of 25-59 years, the positive rates in other groups were lower. The result of Pearson's X2 test showed that there were statistically significant differences in the positive rates of the antibodies among different age groups. Of 329 sera positive for antibody to 2008 -2009 seasonal influenza vaccine virus A/Brisbane/59/ 2007 (H1N1), 31 had anti-A/HlNl antibodies, and of 75 sera negative for antibody to A/Brisbane/59/ 2007(H1N1), 6 had anti-A/HlNl antibodies. The result of Pearson's X2 test showed that there were no significant differences in positive rates of antibody to A/H1N1 between the two types of population. Conclusions The anti-A/HlNl levels in Shanghai population are low, and people are generally susceptible to A/H1N1. The sera positive for antibody to A/Brisbane/59/2007(H1N1) can not provide cross-protection against A/H1N1.     

11-酮基-△9-炔诺酮的合成

We have introduced a carbonyl group at the 11-position and a double bond at the 9-position of norethisterone in order to increase its antifertility potency. The starting material for the preparation of 11-keto-Δ⁹-noret-histerone(9) was 19-hydroxy-Δ⁴-androstene-3,17-dione(1), which was converted to the title compound by partial synthesis through the sequence of reactions:(1)→(9).11-Keto-Δ⁹-norethisterone was found to possess very potent antifertility effect by preliminary screening tests.     

16-(m-氯苯氧基)-17,18,19,20失四碳前列腺素F2α的全合成

A simplified synthetic method for compound (1) was described. Both α,β-unsaturated ketone and y-lactone of (4)b were reduced with Dibal simultaneously to corresponding allylic hydroxy group and γ-lactol in good yield. Without protecting the hydroxy group, the mixture (6) was transformed to the target compound (1) by the known method.     

4-硝基二苯醚-4′-硫代氨基甲酰胺类化合物的合成及其抗日本血吸虫作用

Ten 4-nitrodiphenylether-4′-thiocarbamides were synthesized from 4-nitro-4′-thiocyanodiphenylether and corresponding amines. Preliminary screening data in table 1 showed that most of them exhibited insignificant or low activity against schistosoma japonicnm in mice, while V₉ with a diethyl substituted nitrogen in thiocarbamide structure was found to possess antischistosomal activity as high as that of nithiocyamine (Amoscanatec₉₃₃₃ GO/COP 4540).     

双(2,6-哌嗪二酮)类抗肿瘤药物的研究:2,3-二乙酰氧基-1,4-二(3′,5′-二酮-N4′-取代哌嗪甲基)苯的合成

Seventeen compounds having the structure of 2,3-diacetoxy-1,4-bis(3′,5′- dioxo-N⁴′-substituted piperazinyl methyl)benzene were designed and synthesized based on chelation hypothesis. Their antitumor activities on P388 cells,Hep cells and SGC 7901 cells in vitro were tested. Preliminary results showed that compound 4e has potent antitumor effect against P388 cells and.Hep cells in vitro.     

铀促排药物研究:Ⅳ,N,N′-双-[N-羧甲基-(2,3-二羟基-5-甲氧羰基苄胺乙酰基]-α,ω-二胺的合成

随着核工业的迅速发展,核燃料铀对人类构成了一种潜在威脅。铀在人体脏器内的沉积不但引起损伤,并能诱发肿瘤。关于铀的促排解毒药物,虽有一些报道,但未见在临床应用。作者等曾合成了多个系列新的膦酸类和邻苯二酚类双取代或单取代胺羧酰胺螫合剂,动物试验结果表明其中的大多数排铀效果显著,尤其是邻苯二酚类单取代胺羧酰胺(Ⅰ)中,若干化合物排铀效果远远超过文献报道较多的钛铁试剂和Phosphicine,而且显示了     

邻苯二酚类对称双酰胺螯合剂对铀的促排和解毒

报道9个邻苯二酚类对称双酰胺螯合剂对铀的促排作用,实验证明这些螯合剂均具有一定的促排铀的效果,其中86号化合物促排效果最好,大白鼠肌肉注射500mg·kg~(-I),48h尿铀排出量与对照组相比,比值为2.87;并可显著提高大白鼠铀中毒致死剂量,延迟4h给药,仍然有效;也可使小白鼠铀中毒LD_(50)提高14倍。     

吡酮酸类抗菌药物的研究——Ⅵ.7-氯-6-氟-1-乙基-1,4-二氢-4-氧吡啶(2,3-c)并哒嗪-3-羧酸及其衍生物的合成与抗菌活性

由2,6-二氯-5-氟-3-氰基吡啶出发,经氰基水解、酰氯化、与重氮乙酸乙酯缩合、重氮基还原、环化五步反应合成了一个新的杂环体系,即取代的吡啶(2,3-c)并哒嗪Ⅵ。由Ⅵ为原料经不同途径制得21个新衍生物,其中10个游离酸进行了体外抗菌活性筛选。对金葡-15、大肠-1515、绿脓-29的MIC(μg/ml),除化合物Xa和Xb对大肠-1515为50外,其余均大于100。     

双酚酰胺丁酸及其类似物对铀的促排和解毒

本实验研究邻苯二酚单取代胺羧酰胺类螯合剂对铀的促排解毒作用。实验证明１８个该类螯合剂均有一定的促排作用，４８ｈ尿铀排出量与对照组相比，比值在１．２１～２．５１之间，其中双酚酰胺丁酸（Ｎｏ．１６）促排效果最好，大白鼠ｉｍ０．２５ｇ·ｋｇ－１，尿铀比值达２．５１，ｉｇ０．５ｇ·ｋｇ－１或１ｇ·ｋｇ－１也可提高尿铀排出量。解毒试验表明小白鼠ｓｃ双酚酰胺丁酸使铀中毒ＬＤ５０提高到１６．４倍，ｉｇ给药可提高到７．６倍；大白鼠ｉｇ给药可使铀中毒ＬＤ５０提高到３．９倍；延迟４ｈｉｇ仍然有效。此外双酚酰胺丁酸可显著降低小白鼠因ＮｉＣｌ２、ＭｎＣｌ２、ＣｏＣｌ２中毒引起的死亡数。     

Three new and two rare furanoeremophilanes from senecio asirensis

Three new furanoeremophilanes have been obtained from the aerial parts of Senecio asirensis (N. O. Asteraceae), and characterized as 6-hydroxylmethyl-9-methoxyl-4,11-dimethylnaphtho[2,3-b]furan, designated asirensane-a (1), 6-hydroxyl-1,2-dimethoxyl-4,6,11-trimethyl-6-hydronaphtho[2,3-a]furan-7-one, named asirensane-b (2), and (6,12-dihydroxyl-9-methoxyl-4-methyl-11-acetyl-3,4-dihydronaphtho[2,3-b]furan-3-yl)methyl (2′Z)-2′-methylbut-2′-enoate, designated asirensane-c (3). In addition, two rare furanoeremophilanes have also been isolated and characterized from this source, namely 9-methoxyl-4,11-dimethylnaphtho[2,3-b]furan, named 14-nordehydrocalohastine (4), and 4,11-dimethylnaphtho[2,3-b]furan-6,9-dione, designated as maturinone (5). Their structures have been elucidated on the basis of spectral analysis. The alcoholic extract was also tested for anti-inflammatory activity, which decreased edema by 22% at a dose of 500?mg?kg^-1 after 3?h with respect to the control group treated only with carrageenan, while the standard drug phenylbutazone showed a 50% decrease at a dose of 100?mg?kg^-1, indicating that the extract has moderate anti-inflammatory activity.     

银柴胡的化学成分

目的对石竹科植物银柴胡(Stellaria dichatomaL.var.lanceolataBge.)干燥根银柴胡提取物的化学成分进行分离和结构鉴定。方法银柴胡的乙醇提取物经过氯仿正丁醇水萃取,正反相硅胶柱色谱和HPLC分离,最终分离得到10个化合物,应用核磁共振技术鉴定了其结构。结果10个化合物分别被鉴定为5羟甲基糠醛(5(hydroxymethyl)2 furfural,Ⅰ)、5羟甲基2甲酰基吡咯(5(hydroxymethyl)2 formyl pyrrole,Ⅱ)、香草醛(vanillin,Ⅲ)、香草酸(vanillic acid,Ⅳ)、1(4羟基3甲氧基苯基)乙酮(1(4 hydroxy 3 methoxyphenyl)ethanone,Ⅴ)、1(3′甲氧基4′5′甲叉基二氧)苯基丙醇(1 hydroxy 1(3′methoxy 4′5′methylenedioxy)phenylpropanol,Ⅵ)、二氢阿魏酸(dihydroferulic acid,Ⅶ)、3,4二甲氧基苯丙烯酸(3,4 dimethoxycinnamic acid,Ⅷ)、7烯豆甾醇3棕榈酸酯(stigmast 7 en 3 ol palmitate,Ⅸ)、5,7二羟基二氢黄酮(pinocembrin,Ⅹ)。结论化合物Ⅰ、Ⅲ~Ⅷ、Ⅹ为首次从该属植物中分离得到。     

栽培甘草地上部分化学成分研究

目的对栽培甘草地上部分的化学成分进行研究。方法溶剂法和色谱法分离化合物,光谱法鉴定其结构。结果分离得到7个脂肪族类化合物,分别鉴定为十一烷酸-2-对羟基苯基乙酯[undecanoicacid,2-(4-hydroxyphenyl)ethylester](),1-二十二烷酸甘油酯(docosanoicacid,2,3-dihydroxypropylester)(),1-二十四烷酸甘油酯(tetracosanoicacid,2,3-dihydroxypropylester)(),1-二十二烷酸-2,3-异亚丙基甘油酯[docosanoicacid,(2,2-dimethyl-1,3-dioxolan-4-yl)methylester](),1-(22-羟基二十二烷酸)甘油酯(docosanoicacid,22-hydroxy-,2,3-dihydroxypropylester)(),1-(24-羟基二十四烷酸)甘油酯(tetracosanoicacid,24-hydroxy-,2,3-dihydroxypropylester)(),棕榈酸(palmiticacid)()。结论化合物为新化合物,化合物～为该属植物首次分离,化合物为该种植物首次分离。     

2-取代-1,4-苯骈二氧六环化合物的合成

2-卤代甲基-1,4-苯骈二氧六环与各种仲胺作用,制成2-取代氨甲基衍生物,与肼作用则生成N,N-双-(1,4-苯骈二氧六环-2-甲基)-肼;从2-羟甲基-1,4-苯骈二氧六环与各种酰氯制得相应酯,与β-二甲氨基氯乙烷在钠作用下缩合,得到相应β-氨基醚;从1,4-苯骈二氧六环-2-甲酰氯与β-取代氨基乙醇或胺,制得相应的β-取代氨基乙醇酯及酰胺。     

Photolysis of 3-methyl- and 3-phenyl-4-amino-2-methyl-1-phenyl-3-pyrazolin-5-one (author's transl)

Photolysis of 3-Methyl- and 3-Phenyl-4-amino-2-methyl-phenyl-3-pyrazolin-5-one During the irradiation of aqueous solutions of 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one ( 1d ) besides the compounds 2 and 3 characteristic photolysis products of pyrazolones (Type I), the compound 12 is obtained, which was formed from two molecules of 1d . 4-Amino-2-methyl-1,3-diphenyl-3-pyrazolin-5-one, however isomerises to 8, which upon further irradiation fragments into several components two of them being N-phenyloxamide and N,N′-diphenyloxamide.