合成4-叔丁基-4′-甲氧基二苯甲酰甲烷的新方法

对叔丁基苯甲醛与对甲氧基苯乙酮在甲醇钠作用下缩合生成1-(4-甲氧基苯基)-3-(4-叔丁基苯基)-2-丙烯-1-酮(1,收率91%);1经溴加成,甲醇钠脱溴合成4-叔丁基4′-甲氧基二苯甲酰甲烷(收率89%),总收率81%,其结构经UV-Vis和1H NMR表征.     

(S)-(-)-5-对苄氧基苄基-2,4-噁唑烷二酮的合成

L-酪氨酸经O-苄基化和重氮化反应得到关键中间体--手性3-(对苄氧基苯基)-α-羟基丙酸(4); 4经酯化、氨化和环化反应合成了(S)-(-)-5-对苄氧基苄基-2,4-噁唑烷二酮,总收率10%, 95.4%e.e.,其结构经1H NMR和HR-MS表征.     

5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基吡唑-3-羧酸的合成

对氯苯丙酮经三甲基氯硅烷保护后与草酸单乙酯单酰氯缩合制得4-(4-氯苯基)-3-甲基-2,4-二氧代丁酸乙酯(4);4与2,4-二氯苯肼盐酸盐缩合成腙、再经分子内环合、水解合成了制备利莫那班的关键中间体——5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基吡唑-3-羧酸,总收率30.3%,其结构经1HNMR和MS确证。     

合成4-氯-7-甲氧基-6-硝基喹唑啉的工艺改进

以2-氨基-4-氯苯甲酸为原料,经环合、硝化、甲氧基化和氯代反应合成了4-氯-7-甲氧基-6-硝基唑啉,总收率42.8%,其结构经1H NMR和MS确证。     

(Z)-3,3-二甲基-1-(1H-1,2,4-三唑-1-基)-2-丁酮肟(5-芳基-1,3,4-噁二唑-2-基)甲基醚的合成和抑菌活性

以3,3-二甲基-1-（1H-1,2,4-三唑基）-2-丁酮肟为原料,经醚化、肼解及腙化3步反应得到（E）-N'-（取代苯亚甲基）-2-[（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）丁基-2-亚甲氨氧基]乙酰肼（3a~3u）,化合物3与二乙酸碘苯（IBD）反应,合成了21个（Z）-3,3-二甲基-1-（1H-1,2,4-三唑-1-基）-2-丁酮肟-（5-芳基-1,3,4-噁二唑-2-基）甲基醚（4a~4u）,化合物4的化学结构经核磁共振谱、高分辨质谱和元素分析确证.采用单晶X射线衍射仪测定了化合物4c的晶体结构.抑菌活性测试结果表明,在500 mg/L浓度下,化合物4k,4f,4j和4n对纹枯病菌的防效率分别为70.9%,60.2%,60.0%和60.6%;在25 mg/L浓度下,化合物4b,4c,4d和4e对菌核病菌的抑制率为71.8%~76.9%.     

2,3-二甲基-4-氯吡啶-N-氧化物的合成工艺改进

对2,3-二甲基-4-氯吡啶-N-氧化物(4)的合成工艺进行了改进。以2,3-二甲基吡啶为原料,经氧化(钨酸钠为催化剂,双氧水为氧化剂,收率96.5%),硝化(65%的浓硝酸为硝化剂,收率86.3%,纯度99.0%)及氯化(乙酰氯为氯化剂,收率86.8%,纯度98.6%)合成了4,总收率72.2%,4的结构经1H NMR表征。     

2-(2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-(1,2,4-三唑-1-甲基)-1,3-二氧戊环的合成与杀菌活性

以对羟基苯乙酮为原料,经醚化、Claisen重排、环合得2,2-二甲基-5-乙酰基-2,3-二氢苯并呋喃(4a).2,2-二甲基-5-乙酰基-2,3-二氢苯并呋喃(4a~4c)经卤代、缩酮化、取代反应得12种2-(2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-(1,2,4-三唑-1-甲基)-1,3-二氧戊环(1a~1l).化合物经NMR,元素分析等确证结构,并测试了其对7种植物病菌的抑制活性,结果显示化合物1a,1b,1e,1f,1g和1l对油菜菌核病菌的抑制率均大于70%(25 mg/L),化合物1a和1b对小麦白粉病菌杀灭活性较好,抑制率均为80.0%(500 mg/L).     

4-对羟基苯基-2-丁酮的合成

以生物质来源的对甲氧基苯甲醛(大茴香醛)为原料,经还原反应制备得到对甲氧基苄醇,经氯代反应制备得到对甲氧基氯苄,再与乙酰乙酸乙酯经取代反应制备得到2-乙酰基-3-(4-甲氧基苯基)丙酸乙酯,再经串联的水解、脱羧反应制备得到4-(4-甲氧基苯基)-2-丁酮,最后经脱甲基反应制备得到4-对羟基苯基-2-丁酮,总收率为60.7%。具有路线简捷、易于操作、环境友好、收率高等优点。     

反-4-羟甲基哌啶-3-醇的合成

以4-羟甲基吡啶为原料,经苄基保护、硼氢化钠的还原、硼氢化氧化和脱苄基保护等四步反应得到新型5-羟色胺受体激动剂的关键中间体反-4-羟甲基哌啶-3-醇。总收率达55. 7%。产物结构经IR、1H NMR和MS分析确证,并对合成工艺进行了优化。     

(2R,4S)-4-甲基-2-哌啶甲酸乙酯的合成

以S-(-)-α-苯乙胺为原料,经一锅法制得1-(1-苄基)-6-乙氧羰基-4-甲基-3,4-二氢哌啶(3),收率58.7%。以10%Pd/C为催化剂,3经催化氢化脱苄合成了4-甲基-2-哌啶甲酸乙酯(4),收率96%;4通过减压分馏得(2R,4S)-4,含量95%,其结构经1H NMR,IR和MS确证。     

手性2-(2-吡啶基)-4-羧乙基-1,3-噻唑烷的合成及应用研究

以分级结晶和柱层析法对手性配体2-(2-吡啶基)-4-羧乙基-1,3-噻唑烷(A)进行了异构体分离提纯。将其与[Rh(COD)Cl]_2制备的原位催化剂用于催化苯乙酮及其它几种芳香酮的不对称硅氢化反应,化学收率达90％左右,光学纯度达80％e.e.左右,噻唑烷环上的C_2构型对催化反应结果无影响,C_4位上酯基的影响也不大。     

Synthesis of 1-(dimethylsulfamoyl)-2- and 5-imidazolecarboxaldehydes. Rearrangement of 1-(dimethylsulfamoyl)-5-imidazole-carboxaldehyde to the 4-carboxaldehyde

Lithiation of 1-(dimethylsulfamoyl)imidazole by n-butyllithium, followed by substitution with dimethylformamide provided 1-(dimethylsulfamoyl)-2-imidazolecarboxaldehyde in 19% yield. When 1-(dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)imidazole was lithiated by sec-butyllithium, followed by methyl formate, there was obtained 1-(dimethylsulfamoyl)-2-(tert-butyldimethylsilyl)-5-imidazolecarbox-aldehyde (57%). Removal of the silyl group by acetic acid yielded 1-(dimethylsulfamoyl)-5-imidazolecarbxaldehyde ( 11 , 96%) as a gum. Isomerization of 11 took place slowly at room temperature (10 days), or faster in tetrahydrofuran solution containing triethylamine (2 hours) to form crystalline 1-(dimethylsul-famoyl)-4-imidazolecarboxaldehyde (12) in 68% yield. Proton and carbon-13 nmr spectra were analyzed to determine the structure of the isomers. However, only X-ray crystallography established the structure of 1-(dimethylsulfamoyl)-4-imidazolecarboxaldehyde, unequivocally. A mechanism for the isomerization of 11 to 12 is proposed.     

(R)-2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚硫酰基}- 1H-苯并咪唑的合成

以2,3-二甲基吡啶为起始原料, 经过11步反应, 不对称合成了质子泵抑制剂的关键中间体: (R)-2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚硫酰基}-1H-苯并咪唑. 研究了用手性高效液相色谱拆分对映体、测定产品光学纯度的方法, 结果表明目标产品的ee值达到99%. 通过IR, UV, MS以及1H NMR分析对重要中间体和目标产品进行了结构鉴定.     

离子色谱法测定乙二胺水溶液中的SO32-、SO42-

用离子色谱法测定5％乙二胺水溶液中的SO3^2-、SO4^2-。选用IonPac柱，以3mmol/L AS11分离碳酸钠－10％甲醇水溶液作为淋洗液，20min内便可完成测定。SO3^2-和SO4^2-的回收率分别为97.6%-101.6%和99.2%-101.0%，相对标准偏差分别为1．31％和1．42％。     

Synthesis and characterization of nadimidized 1-[(dialkoxyphosphinyl)methyl1]-2,4- and -2,6- diaminobenzenes and their polymerization to fire-resistant laminating resins

A series of nadimidized 1-[(dialkoxyphosphinyl1)methyl]-2,4- and -2,6-diaminobenzenes was prepared and polymerized thermally to yield highly crosslinked fire-resistant laminating resins. Bisnadimides were characterized by elemental analysis and Fourier-transform-infrared (FT–IR) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. Curing behavior of the polymer precursors was studied by differential scanning calorimetry (DSC). Char yield of polymers at 700°C was 64–69% and 30–60% in nitrogen and air atmospheres, respectively. The pyrolysis behavior of some bisnadimides was investigated by gas chromatography–mass spectroscopy (GC–MS). Cyclopentadiene was evolved by retrograde Diels–Alder reaction during processing, but most was captured by copolymerization. The fire-resistance of some polymers was evaluated by determining their limiting oxygen index and smoke evolution.     

Synthesis of (-)-7-epiaustraline and (-)-1-epicastanospermine

Highly efficient and selective syntheses of the title compounds are described. The cornerstone of the synthetic plan is the tandem inter [4 + 2]/inter [3 + 2] cycloaddition process. These syntheses differ from previous applications of this strategy in that they incorporate an alkylation in the hydrogenolysis step to close the second ring of the azabicyclic systems. Notable features of the sequence are (1) the highly regio- and stereoselective [3 + 2] cycloaddition of nitronate 15 with siloxymethyl (Z)-beta-silylvinyl ketone (Z)-22b and (2) the highly selective reduction of the resulting ketone 24a with L-Selectride. A single-crystal X-ray structure analysis of synthetic (-)-7-epiaustraline confirmed that the targeted structure was successfully synthesized. This stimulated a reexamination of the structural assignment of the natural product. (-)-1-Epicastanospermine was synthesized in four steps from the common intermediate 27a. The absolute configuration of (-)-1-epicastanospermine was assured by single-crystal X-ray structure analysis of intermediate (-)-27a. Thus, the sign of the optical rotation had to be revised. The overall efficiency of these syntheses were 9 steps and 23% yield for (-)-7-epiaustraline and 10 steps and 20% yield for (-)-1-epicastanospermine     

Fire-resistant polyimides and copolyimides based on 1-[(dialkoxyphosphinyl)methyl]-2,4- and -2,6-diaminobenzenes

Various phosphorus-containing polyimides were prepared by the reaction of 1-[(dialkoxyphosphinyl)methyl]-2,4- and -2,6-diaminobenzenes (1) with a tetracarboxylic dianhydride like pyromellitic dianhydride (PMDA) and benzophenone tetracarboxylic dianhydride (BTDA). In addition, copolyimides that contained approximately 3% phosphorus were prepared by the reaction of 1 and m-phenylenediamine (MPD) with the aforementioned tetracarboxylic dianhydrides. Elemental analysis, inherent viscosity, infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) studies were performed to characterize the polymers. Their thermal properties were compared with those of the corresponding common polyimides. It was shown that the molecular weight and thermal stability of the polymers were reduced as the concentration of the phosphorus moieties increased. The fire-resistance of the copolyimides was evaluated by determining their limiting oxygen index (LOI) value. Copolyimides that contained about 3% phosphorus showed an LOI value approximately 30% higher, than the value of the corresponding common polyimides. In addition, a model diamic acid and diimide was synthesized by the reaction of 1-[di(2-chloroethoxyphosphinyl)methyl]-2,4- and - 2,6-diaminobenzene (DCEPD) with phthalic anhydride and characterized by elemental analysis, IR, proton nuclear magnetic (¹H-NMR) spectroscopy, DSC, and TGA. The pyrolysis behavior of the model compounds was investigated by gas chromatography-mass spectrometry (GC-MS). A direct cleavage of the P? C bond and a possible rearrangement to diisocyanates occurred during their pyrolysis.     

Metabolism of 1-(3-[3-(4-cyanobenzyl)-3H-imidazol-4-yl]-propyl)-3-(6-methoxypyridin-3-yl)-1-(2-trifluoromethylbenzyl)thiourea (YH3945), a novel anti-cancer drug, in rats using the 14C-labeled compound

The metabolism of a novel anti-cancer agent, 1-(3-[3-(4-cyanobenzyl)-3H-imidazol-4-yl]-propyl)-3-(6-methoxypyridin-3-yl)-1-(2-trifluoromethylbenzyl)thiourea (YH3945), was investigated in rats. Bile, plasma, feces, and urine were collected and analyzed by a high-performance liquid chromatography (HPLC) system equipped with ultraviolet (UV), mass spectrometric, and radioactivity detectors. After intravenous dosing, mean radiocarbon recovery was 74.4 +/- 1.3% with 62.4 +/- 1.2% in the feces and 12.0 +/- 0.5% in the urine. Biliary excretion of the radioactivity for the first 24 h period was approximately 32%, suggesting that YH3945 is cleared by hepatobiliary excretion. YH3945 was extensively metabolized to 21 different metabolites including glucuronide conjugates, and structures of the metabolites were elucidated based on MS(n) and NMR spectral analyses. The major metabolic pathways in the rat were identified as O-demethylation of methoxypyridine, N-debenzylation of imidazole, and hydroxylation. Cyclic metabolites were also identified; concomitant demethylation in the methoxypyridine moiety and hydroxylation at the C16 position might destroy the chemical stability of the compound and subsequently lead to non-enzymatic cyclization. Cyclic metabolites were characteristic of YH3945, and a non-enzymatic reaction mechanism for the formation of cyclic metabolites was postulated.     

6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉的合成

以6-溴-3-(氯苯基甲基)-2-甲氧基喹啉(2)为起始原料,经过偶合对接反应合成了新型喹啉类抗结核药物TMC-207的衍生物6-溴-3-[2-(6-溴-2-甲氧基喹啉-3-基)-1,2-二苯乙基]-2-甲氧基喹啉,其结构经1H NMR和HR-MS确证.最佳反应条件:2 10 mmol,Et_3N 5 mL,KI 0.17 g,乙腈150 mL,于80 ℃反应6 h,收率73%.     

1-(4-氯苯胺基)-4-(4-吡啶甲基)-2,3-二氮杂萘琥珀酸盐的合成与抑制肿瘤活性

研究了1-(4-氯苯胺基)-4-(4-吡啶甲基)-2,3-二氮杂萘琥珀酸盐的合成工艺,采用苯酞和吡啶甲醛为起始原料,经加成、重排、取代和成盐4步反应得到目标化合物。 中间体及目标化合物通过1H NMR、MS和HPLC进行了表征。 重结晶纯化后的目标化合物纯度为98.1%。 对荷瘤（人大肠癌HT 29细胞）裸鼠的抑癌活性测定表明,该化合物具有明显的抑制肿瘤生长作用。