L-5-(2-乙酰氧基-丙酰胺基)-2,4,6-三碘异酞酰氯的合成

目的合成标题化合物,并进行改进。方法以5-氨基-2,4,6-三碘异酞酸为原料经酰氯化、酰胺化反应制得目标化合物。结果总收率达95.4%,目标化合物的结构经红外光谱和元素分析确证。结论改进的路线操作简便,易于控制,缩短了反应时间,降低了生产成本,更易于工业化生产。     

L-5-(2-乙酰氧基-丙酰胺基)-2,4,6-三碘异酞酰氯的合成

目的合成标题化合物,并进行改进。方法以5-氨基-2,4,6-三碘异酞酸为原料经酰氯化、酰胺化反应制得目标化合物。结果总收率达95.4%,目标化合物的结构经红外光谱和元素分析确证。结论改进的路线操作简便,易于控制,缩短了反应时间,降低了生产成本,更易于工业化生产。     

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％。     

5—甲氧基乙酰胺基—2，4，6—三碘异酞酰氯的合成

以间苯二甲酸为原料,经硝化、还原、碘化、酰氯化、酰胺化制得碘普安中间体5－甲氧基乙酰胺基－2,4,6－三碘异酞酰氯,总收率为41．9％。     

配基部分含保护了氨基的半乳糖苷衍生物的合成

目的：研究配基部分含氨基的半乳糖苷衍生物的合成。方法：均以氨基乙醇为原料,经用三氟乙酰基或苄氧羰酰基保护氨基,磺酰化和碘取代后,分别和已知的2－S－（2,3,4,6）－四－O－乙酰基β-D－半乳吡喃糖基－2－异硫脲氢溴酸盐作用生成目标物。结果：化合物的结构经IR,^1HNMR和元素分析确证。结论：此两种方法都是合成配基部分含保护了氨基的半乳糖苷衍生物的较好方法。     

β-内酰胺酶抑制剂他唑巴坦的合成

目的：合成他唑巴坦。方法：以6－氨基青霉烷酸（6－APA）为原料，经溴化，酯化，氧化并脱溴成亚砜后，与三唑反应，再氧化，脱保护基得他唑巴坦。结果：使用30％双氧水氧化生成亚砜，与2－三甲基硅－1，2，3－三唑反应生成2α－甲基－2β－（1，2，3－三唑－1－基）甲基青霉烷－3α－羧酸二苯甲酯，结论：该方法缩短了反应路线，操作简便，总收率24％。     

2-正丁基-1,3-二氮杂螺[4,4]壬-1-烯-4-酮的合成

目的：合成2－正丁基－1，3－二氮杂螺[4,4]-壬－1－烯－4－酮。方法：以环戊酮合成的1－氨基环戊酸为起始原料。结果：1－氨基环戊酸经过酯化，与戊亚氨酸乙酯缩合得目标化合物。结论：该合成工艺有一定改进。     

2-氨基咪唑硫酸盐的制备

目的：合成2－氨基咪唑硫酸盐。方法：以氨基乙醛缩甲醇制备的N－（2，2－二甲氧基乙基）胍硫酸盐经盐酸催化环合制得2－氨基咪唑硫酸盐。结果：产物结构经^1HNMR确证；溶点与文献一致；收率70％－81．5％。结论：该法成本低，反应条件温和，收率高，易于生产。     

2,4,5-三氨基-6-羟基嘧啶硫酸盐的合成

以氰乙酸甲酯为起始原料，经环合，亚硝化，还原合成2，4，5-三氨基-6-羟基嘧啶硫酸盐。总收率75%。     

(1R,2S)-2-氨基-1-苯基-1-丙醇的合成

目的：改进（1R，2S）－2－氨基－1－苯基－1－丙醇的合成工艺。方法：以苯丙酮为起始原料，经中间体肟基苯丙酮和Pt-Pd/C催化加氢反 应合成赤式2－氨基－1－苯基－1－丙酮，再用S－羧甲基－L－半胱氨酸作拆分试剂进行拆分，得到目标产物。结果：收率和光学纯度有较大提高，总收率达55．5％。结论：该工艺具有工业应用价值。     

The metabolism and excretion of prochloraz,an imidazole-based fungicide,in the rat

1. Following oral administration of prochloraz (1-[N-propyl-N-2-(2,4,6-trichlorophenoxy)ethylcarbamoyl]imidazole) at 100mg/kg body weight to rats, the compound underwent extensive metabolism, the primary route appearing to be opening of the imidazole ring followed by hydrolysis of the alkyl chain. The major metabolites were 2,4,6-trichlorophenoxyacetic acid and 2-(2,4,6-trichlorophenoxy)ethanol, which is present mainly as a glucuronide conjugate. Ring hydroxylation occurred to produce several minor metabolites. No unchanged prochloraz was excreted in the urine.

2. Tissue residues 96?h after dosing were generally < 1?mg prochloraz equivalents/kg tissue. The highest residues were found in the liver (2˙8–5˙1?mg prochloraz equivalents/kg tissue) and kidney (1˙5–2˙1?mg prochloraz equivalents/kg tissue), the principal organs of metabolism and excretion. Residues in female rats were generally slightly higher than those found in males.

3. The metabolites were quantitatively excreted within 96?h, with > 50% of the dosed radioactivity being found in the 0–24?h excreta. Urinary excretion accounted for 65% dose in male and 41% in female rats, respectively.     

Meisenheimer complexes of 2,4,6-trinitro-3-hydroxybenzoic acid (author's transl)

Meisenheimer Complexes of 2,4,6-Trinitro-3-hydroxybenzoic Acid 2,4,6-Trinitro-3-hydroxybenzoic acid (2) in acetone in the presence of 3 mol potassium hydroxide forms a dark red coloured Meisenheimer trinitrocyclohexadienate-tripotassium adduct 3 which is transformed to a red propenide-complex 6a and/or 6b in 0,1 n alkali. In 5 n alkali without addition of acetone the propenide complexes 5a and 5b are formed.     

碘普罗胺的合成

3-氨基-5-(2,3-二乙酰氧基正丙胺基甲酰基)-2,4,6-三碘苯甲酸(6)经与甲氧基乙酰氯反应、碳酸氢钠作用下水解后再经氯代得3-[(2-甲氧基)乙酰胺基]-5-(2,3-二羟基正丙胺基甲酰基)-2,4,6-三碘苯甲酰氯(4),4与N-甲基-2,3-二羟基丙胺反应制得碘普罗胺,总收率为80%(以6计)。     

In vitro characterization of arylhydrazones of active methylene derivatives

Arylhydrazones of active methylene compounds (AHAMCs) are potent chemotherapy agents for the cancer treatment. AHAMCs enhance the apoptotic cell death and antiproliferation properties in cancer cells. In this study, a series of AHAMCs, 13 compounds, was assayed for cytotoxicity, apoptosis, externalization of phosphatidylserine, heterogeneity and cellular calcium level changes. The in vitro cytotoxicity study against HEK293T cells suggests that AHAMCs have significant cytotoxic effect over the concentrations. Top 5 compounds, 5-(2-(2-hydroxyphenyl) hydrazono)pyrimidine-2,4,6(1H,3H,5H)-trione (5), 4-hydroxy-5-(2-(2,4,6-trioxo-tetrahydro-pyrimidin-5(6H) ylidene)hydrazinyl)benzene-1,3-disulfonic acid (6), 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxybenzenesulfonic acid (8), 5-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-4-hydroxybenzene-1,3-disulfonic acid (9) and 2-(2-sulfophenylhydrazo)malononitrile (10) were chosen for the pharmacodynamics study. Among these, compound 5 exhibited the better cytotoxic effect with the IC₅₀ of 50.86?±?2.5?mM. DNA cleavage study revealed that 5 induces cell death through apoptosis and shows more effects after 24 and/or 48?h. Independent validation of apoptosis by following the externalization of phosphatidylserine using Annexin-V is also in agreement with the potential activity of 5. Single cell image analysis of Annexin-V bound cells confirms the presence of mixture of early, mid and late apoptotic cells in the population of the cells treated with 5 and a decreased trend in cell-to-cell variation over the phase was also identified. Additionally, intracellular calcium level measurements identified the Ca²⁺ up-regulation in compound treated cells. A brief inspection of the effect of the compound 5 against multiple human brain astrocytoma cells showed a better cell growth inhibitory effect at micro molar level. These systematic studies provide insights in the development of novel AHAMACs compounds as potential cell growth inhibitors for cancer treatment.     

碘他拉酸的合成

5-硝基-1,3-苯二甲酸单甲酯和40%甲胺水溶液经酰胺化反应得到3-硝基-5-[(甲胺基)羰基]苯甲酸,再经Pd/C催化氢化还原和氯化碘碘代得到3-氨基-2,4,6.三碘-5-[(甲胺基)羰基]苯甲酸,最后经乙酰化反应制得离子型x线造影剂碘他拉酸,总收率约80%.     

Inhibition of papilloma formation by analogues of 7,8-dihydroretinoic acid

The design of analogues of 7,8-dihydroretinoic acid (7,8-dihydro-RA) was based on reported biological activities of this retinoid and its dihydro-TMMP(1) analogue and on structural hypotheses. 7-Oxa-7,8-dihydroretinoids (5, 6) were prepared by O-alkylation of phenoxides by methyl 8-bromo-3,7-dimethyl-2,4,6-octatrienoate. In some cases, C-alkylation also occurred. 7-Aza-8-oxo-7,8-dihydroretinoids (12, 13) were synthesized from benzeneamines and the acyl cyano or bromo derivative of the monomethyl ester of 3,7-dimethyl-2,4,6-octatriene-1,8-dioic acid. These monomethyl ester precursors were synthesized from the known analogous aldehyde via an O-trimethylsilyl cyanohydrin. 7-(2,3,5-Trimethylphenoxy)-3,5-dimethyl-2,4,6-octatrienoic acid (6b) was the most active of the 7-oxa-7,8-dihydro-RAs in inhibiting DMBA-initiated and TPA-promoted mouse-skin papillomas. The ED(50) was about 4-fold that of etretinate. Two additional 7-oxa-7,8-dihydro-RAs exhibited modest activity in the papilloma assay. Some of the 7-oxa-7,8-dihydro-RAs bind to CRABP and RARalpha.     

Metabolism of difebarbamate in man

The metabolism of 1,3-bis(3-butoxy-2-carbamoyloxypropyl)-5-ethyl-5-phenyl- (1H,3H,5H)-pyrimidine-2,4,6-trione (difebarbamate) in man was studied. Human volunteers received a single oral dose of 25 mg/kg difebarbamate. Urine was extracted with Amberlite XAD-2 resin and the extracts were separated by preparative HPLC after enzymatic hydrolysis. Four major metabolites were isolated and their structures were determined using NMR and mass spectrometry. The oxygen dealkylation led to the formation of two metabolites: 1-(3-butoxy-2-carbamoyloxypropyl)-3-(2-carbamoyloxy-3-hydrox ypropyl)-5-ethyl-5- phenyl-(1H, 3H, 5H)-pyrimidine-2,4,6,-trione and 1,3-bis(2-carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H )- pyrimidine-2,4,6,-trione. The hydrolysis of the carbamoyloxy group with the oxygen dealkylation led to the formation of 1-(2-carbamoyloxy-3-hydroxypropyl)-3-(2,3-dihydroxypropyl)-5-ethyl - 5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6,-tione, whereas the 4-hydroxylation of the benzene ring together with the oxygen dealkylation led to the formation of 1,3-bis(2-carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-(4-hydroxyphenyl )-(1H,3H,5H)- pyrimidine-2,4,6,-trione. No traces of the parent drug were found.     

Metabolism of an imidazole fungicide (prochloraz) in the rat after oral administration.

The metabolic fate and pathway of the imidazole fungicide prochloraz (1-[N-propyl-N-2-(2,4,6-trichlorophenoxy) ethyl carbamoyl] imidazole) were investigated in the rat after administration of oral single doses with radiolabelled molecules. At both dose levels (50 and 250 mg/kg body weight), virtually all of the ingested [14C-phenyl]prochloraz was excreted in the urine or faeces within 96 hr, the bulk of excretion occurring between 24 and 48 hr after dosing. Urinary elimination accounted for 61 and 68% of the respective initial doses. Urinary metabolic products were isolated and identified by thin-layer chromatography, gas chromatography or gas chromatography coupled with mass spectrometry analysis. Prochloraz was completely metabolized with no unchanged compound being excreted in the urine. The main biotransformation products in rat urine were 2,4,6-trichlorophenoxyacetic acid and its corresponding alcohol, the latter as a glucuronic acid conjugate. Ring hydroxylation also occurred, with the hydroxy-2,4,6-trichlorophenoxyethanol and hydroxy-2,4,6-trichlorophenoxyacetic acid metabolites excreted in small amounts in the urine. 2,4,6-Trichlorophenol and unconjugated 2,4,6-trichlorophenoxyethanol were identified as minor urinary metabolites.     

碘昔兰的合成

5-乙酰胺基-3-[（2-羟乙胺基）羰基]-2,4,6-三碘苯甲酸经N-烷基化、乙酰化、酰氯化、酰胺化和水解反应制得非离子型X-射线造影剂碘昔兰,总收率约44%.     

Polyamide microcapsules containing jojoba oil prepared by inter-facial polymerization

Jojoba oil containing polyamide microcapsules having diameter of ～5?µm were prepared by inter-facial polycondensation by direct method (oil-in-water). Qualitative effects of both the formulation and the process parameters on microcapsules characteristics were investigated by SEM observations. Morphological analysis showed the dependence of the external membrane compactness on the chemical nature of the water-soluble polyamine and the oil-soluble acid polychloride: 1,6-hexamethylenediamine (HMDA) and terephthaloyl dichloride (TDC) were found to favour the production of smooth and dense surfaces. The use of ultrasonic irradiations during the dispersion step to get a further reduction of microcapsules size was also evaluated.