新型双烯丙基化手性二胺的合成

通过烯丙基溴化锌对手性亚胺的两次不对称加成, 合成了光活性的双烯丙基化的新型手性二胺. 首先经N-Boc保护和Dess-Martin氧化制得了光活性的(S)-N-Boc-3-苯基-2-氨基丙醛. (S)-N-Boc-3-苯基-2-氨基丙醛与(S)-缬氨基酸甲酯缩合生成手性亚胺, 在七水合三氯化铈(CeC1₃•7H₂O)催化以及底物的手性诱导作用下, 该手性亚胺与烯丙基溴化锌经不对称加成反应合成了高光活性的单烯丙基化手性胺. 该手性胺与2-噻吩甲醛缩合生成新的手性亚胺, 再次通过不对称烯丙基加成反应合成了含有四个手性中心的高光学纯的双烯丙基化手性二胺. 目标化合物和关键中间体的结构均被¹H NMR, ¹³C NMR及MS确证.     

新型手性N,N′-双支套索冠醚的合成及其应用

(S)-苯丙氨醇和原氯乙酸三乙酯作用得到的手性酰胺醇和手性噁唑啉分别与1,7-二氮-12-冠-4反应, 得到了两种手性N,N′-双支套索冠醚N,N′-二[(S)-N-(1-羟甲基-2-苯基乙基)乙酰胺-2]-1,7-二氮-12-冠-4 (1a)和N,N′-二[(S)-4-苄基-噁唑啉-2-亚甲基]-1,7-二氮-12-冠-4 (1b). 前者应用于D/L-肉碱的手性分离; 后者的铜配合物用于重氮醋酸酯对烯烃的不对称环丙烷化反应.     

改性Ultrastable-Y分子筛固定化对非水相中脂肪酶拆分(R,S)-2-辛醇的影响

采用改性Ultrastable-Y分子筛固定Penicillium expansum PED-03 脂肪酶(PEL), 利用固定化PEL在非水相中对(R,S)-2-辛醇进行手性拆分, 考察了改性Ultrastable-Y分子筛固定化处理对PEL催化性能的影响. 结果表明, 与游离PEL及经其它载体固定化的PEL相比, 改性Ultrastable-Y分子筛固定的PEL所催化的拆分反应的转化率(c)和对映体过量值(ee)以及对映体选择性(E)均得到了较大提高. 经固定化处理后, PEL的最适反应温度明显升高, 适宜反应温度范围变宽, 其稳定性也得到了明显改善, 而适宜反应pH值则具有“记忆”性. 在间歇式反应器中利用Ultrastable-Y分子筛固定化PEL对(R,S)-2-辛醇进行手性拆分, 50 ℃反应24 h转化率(c)可达理论值的97.68%, 对映体过量值(ee)可达98.75%. 连续8批拆分反应的结果表明: 改性Ultrastable-Y分子筛固定化脂肪酶催化效率高、立体选择性强(平均E 值＞460), 且催化性能稳定, 显示了该固定化酶在(R,S)-2-辛醇的手性拆分方面具有良好的应用前景.     

手性硼酸酯介入的不对称合成3† (R)-或(S)-1,1'-联-2-萘酚硼酸-(S)-脯氨酸酐促进的前手性亚胺的不对称硼烷还原

手性螺硼酸酯(R)-或(S)-1,1'-联-2-萘酚硼酸-(S)-脯氨酸酐[(R,S)-1或(S,S)-1]对前手性亚胺硼烷还原的不对称催化活性被观察到. 在(R,S)-1或 (S,S)-1存在下, 由前手性二烷基酮或烷基苯酮与苯胺缩合生成的前手性亚胺在THF中被硼烷还原, 高产率地给出手性仲胺, 其对映体纯度高达74% ee. 其中, 三种手性仲胺[N-(2-戊基)苯胺, N-(3-甲基-2-丁基)苯胺和N-(4-甲基-2-戊基)苯胺]系首次合成.     

(S)-和(R)-普萘洛尔的不对称合成

普萘洛尔是一种临床上广泛使用的β受体阻断剂, 介绍了一种不对称合成(S)-和(R)-普萘洛尔的方法. 以手性Salen-Co^III催化剂水解动力学拆分外消旋环氧氯丙烷得到高光学纯度的(S)-环氧氯丙烷和(R)-3-氯-1,2-丙二醇, 以(S)-环氧氯丙烷为手性原料先水解得(S)-3-氯-1,2-丙二醇, 其与1-萘酚反应得(S)-3-(1-萘基)-丙烷-1,2-二醇, 再与氯化亚砜反应得环状亚硫酸酯, 最后和异丙胺作用得(S)-普萘洛尔, 总收率80.9%, 光学纯度大于99%; 而同样以(S)-环氧氯丙烷为手性原料直接与1-萘酚反应得(2R)-3-(1-萘氧基)-1,2-环氧丙烷, 再与异丙胺作用得(R)-普萘洛尔, 总收率74.5%, 光学纯度大于99%.     

理论研究H原子与SiHF3的抽提反应

对H和SiHF₃的反应进行了详细的理论研究. 用从头算(UMP2)方法研究了其机理, 结果表明抽提氢是惟一可行的反应通道, 抽提氟的通道由于具有较高的势垒而难以进行. 用变分过渡态理论加小曲率隧道效应对该反应进行了动力学研究, 得到200~3000 K温度范围内的速-温关系式为: k(T) = (9.74×10^-22)T ^{3.22exp(-856/T).}     

α-亚胺酮的不对称转移氢化合成(R)-沙丁胺醇

用手性(S,S)-Ru-TsDPEN催化剂不对称转移氢化α-亚胺酮化合物5-[(1,1-二甲基乙基)亚胺基]乙酰基-2-羟基苯甲酸甲酯(2)得光学纯β-氨基芳基乙醇类化合物(R)-5-[2-[(1,1-二甲基乙基)氨基]-1-羟乙基]-2-羟基苯甲酸甲酯(3), 再经一步还原反应即得(R)-(－)-沙丁胺醇. 对反应关键一步α-亚胺酮的不对称转移氢化反应条件进行了研究.     

4(R)-(2,4,6-三甲基苄氧基)-(S)-脯氨酸促进的直接不对称羟醛反应

方便地合成了一种新的不对称羟醛反应的手性催化剂4(R)-(2,4,6-三甲基苄氧基)-(S)-脯氨酸. 以过量的丙酮作溶剂, 使用5 mol%该催化剂, 有效地催化了多种取代苯甲醛与丙酮间的不对称羟醛反应, 产率最高达91.0%, ee最高达84.3%.     

联苯类手性双膦配体的合成方法改进

从易获得的间溴苯甲醚出发, 利用改进后的方法经六步反应合成了手性双膦配体(R)-和(S)-6,6-二甲氧基-2,2-二(二芳基膦基)-1,1'-联苯[(R)-和(S)-6], 改进后的方法简化了合成步骤, 提高了收率, 可方便地用于在苯环上具有不同取代基的联苯类手性双膦配体衍生物的合成.     

七-(2,6-二-O-甲基)-β-环糊精对1,1'-联萘酚对映体手性识别的电喷雾质谱研究

利用电喷雾质谱研究了β-环糊精、七-(2,6-二-O-甲基)-β-环糊精作为手性识别试剂对1,1'-联萘酚对映体的手性识别效应. 实验结果表明, 在气相中, β-环糊精与七-(2,6-二-O-甲基)-β-环糊精都可以与联萘酚形成非共价复合物. 对形成的复合物的串联质谱研究表明, β-环糊精不能识别联萘酚对映体, 而七-(2,6-二-O-甲基)-β-环糊精对联萘酚对映体有较强的手性识别效应. 进一步研究表明七-(2,6-二-O-甲基)-β-环糊精与联萘酚对映体混合比例以及CID能量对于手性识别并无影响.     

HPLC determination of andrographolide in rat whole blood: study on the pharmacokinetics of andrographolide incorporated in liposomes and tablets

A sensitive and simple high-performance liquid chromatographic method with UV detection was developed and validated for the determination of andrographolide in rat whole blood. Carbamazepine was employed as internal standard and the blood sample was extracted with chloroform. Chromatographic separations were achieved on a Chromasil ODS column (250 x 4.6 mm, 5 microm). The mobile phase was consisted of methanol-water (52:48, v/v) and delivered at 0.8 mL/min. The detection wavelength was set at 225 nm. The calibration curve had a good linearity in the range 0.053-530 microg/mL in rat whole blood with its correlation coefficient being 0.996. The extraction recovery of andrographolide was ranged from 65.7 to 72.6%. The intra-day and inter-days repeatabilities were below 4.2% in terms of the percentage of relative standard deviation (RSD). The method was used to provide data on the pharmacokinetics of the drug in rats. The data obtained was processed using the 3P87 pharmacokinetic program. The results showed that the disposition of andrographolide after intravenous administration of liposomal andrographolide conformed to a two-compartment open model with alpha = 4.75 x 10(-2) +/- 2.41 x 10(-3) min(-1), beta = 3.16 x 10(-3) +/- 1.58 x 10(-4) min(-1), V(c) = 174.67 +/- 13.97 mL, k(21) = 1.60 x 10(-2) +/- 8.12 x 10(-4) min(-1), k(10) = 9.38 x 10(-3) +/- 5.62 x 10(-4) min(-1), k(12) = 2.53 x 10(-2) +/- 1.27 x 10(-3) min(-1) and AUC(0-infinity) = 1525.47 +/- 92.35 microg min/mL. For the intragastric administration of andrographolide tablets, the disposition of andrographolide followed a one-compartment open model with k(e) = 6.78 x 10(-3) +/- 3.53 x 10(-4) min(-1), k(a) = 3.69 x 10(-2) +/- 4.68 x 10(-3) min(-1), T(max) = 59.69 +/- 3.61 min, C(max) = 1.62 +/- 0.11 microg/mL, V(c) = 1056.90 +/- 83.42 mL, AUC(0-infinity) = 348.75 +/- 24.41 microg min/mL.     

Evaluation of luminol-H(2)O(2)-KIO(4) chemiluminescence system and its application to hydrogen peroxide, glucose and ascorbic acid assays

A novel chemiluminescence (CL) system was evaluated for the determination of hydrogen peroxide, glucose and ascorbic acid based on hydrogen peroxide, which has a catalytic-cooxidative effect on the oxidation of luminol by KIO(4). Hydrogen peroxide can be directly determined by luminol-KIO(4)-H(2)O(2) CL system. The detection limit was 3.0x10(-8) mol l(-1) and the calibration graph was linear over the range of 2.0x10(-7)-6.0x10(-4) mol l(-1). The relative standard deviation of H(2)O(2) was 1.1% for 2.0x10(-6) mol l(-1) (N=11). Glucose was indirectly determined through measuring the H(2)O(2) generated by the oxidation of glucose in the presence of glucose oxidase at pH 7.6. The present method provides a source for H(2)O(2), which, in turn, coupled with the luminol-KIO(4)-H(2)O(2) CL reaction system. The CL was linearly correlated with glucose concentration of 0.6-110 mug ml(-1). The relative standard deviation was 2.1% for 10 mug ml(-1) (N=11). Detection limit of glucose was 0.08 mug ml(-1). Ascorbic acid was also indirectly determined by the suppression of luminol-KIO(4)-H(2)O(2) CL system. The calibration curve was linear over the range of 1.0x10(-7)-1.0x10(-5) mol l(-1) of ascorbic acid. The relative standard deviation was 1.0% for 8.0x10(-7) mol l(-1) (N=11). Detection limit of ascorbic acid was 6.0x10(-8) mol l(-1). These proposed methods have been applied to determine glucose, ascorbic acid in tablets and injection.     

Asymmetric synthesis of 4-deoxyverrucarol via two types of ring expansion reactions

Asymmetric synthesis of a trichothecane analogue, 4-deoxyverrucarol (2), was carried out through two types of ring expansion reactions. First, synthesis of the racemate of 2 was investigated. Thus, 1-[1-(tert-butyldimethylsiloxy)-ethyl]-1-methoxycarbonyl-2-hexen-4-on e (10), prepared by Diels-Alder reaction, was converted into the cyclopropylidene 15. The cyclobutanone (+/-)-18 was obtained from 15 via dihydroxylation, followed by successive treatments with SO(2)Cl(2) in the presence of imidazole and Florisil. After transformation of (+/-)-18 into the vinylcyclobutanol (+/-)-19, the second ring expansion reaction was performed with Pd(OAc)(2) to provide the cyclopentanone (+/-)-20. The product was converted into the racemate of 4-deoxyverrucarol (2) through the cyclohexenone (+/-)-22, but the diastereoselectivity during the introduction of the double bond was unsatisfactory. The selectivity was improved in the case of the asymmetric synthesis. The optically active cyclobutanone (+)-18 was prepared via AD reaction of 15 with 73% ee. After the transformation of (+)-18 into the cyclohexanone (-)-30 through the palladium-mediated ring expansion reaction, (-)-30 was subjected to the diastereoselective deprotonation reaction using the chiral amide. The key synthetic intermediate (-)-25 of 4-deoxyverrucarol (2) was synthesized in an optically pure form by taking advantage of a kind of kinetic resolution that occurred during the deprotonation step.     

螺环三代树形大分子化合物的合成

以对苯二甲醛单缩醛与季戊四醇反应得到了2,4,8,10-四氧杂-2,9-二(4-二氰基乙烯基苯基)螺[5.5]十一烷(1), 经水解, 再与丙二腈反应, 制备了中间体2,4,8,10-四氧杂-2-(4-二氰基乙烯基苯基)-9-(4-甲酰基苯基)螺[5.5]十一烷(3). 8-(4-氧代环己烷基)-1,4-二氧杂螺[4.5]癸烷经芳构化形成2,6,10-三-(4-氧代环己烷基)-1,2,3,4,5,6,7,8,9,10,11,12-十二氢苯并[l]菲(4), 再与甲醛进行羟醛缩合, 制成了2,6,10-三-(4-羟基-3,3,5,5-四羟甲基环己烷基)-1,2,3,4,5,6,7,8,9,10,11,12-十二氢苯并[l]菲(5), 将5与过量的3反应, 得到了目标树形大分子化合物2,6,10-三-{15-(3,11-二(-4-(3-((9-(4-二氰基乙烯基)苯基)2,4,8,10-四氧杂螺[5.5]十一烷基)))-7-羟基-二螺[5.1.5.3]十六烷基)}-1,2,3,4,5,6,7,8,9,10,11,12-十二氢苯并[l]菲(6), 收率为18.1%. 产品结构经IR, 1H NMR, MS和元素分析进行了表征. 对影响反应的因素进行讨论.     

Chlorine dioxide-facilitated oxidation of the azo dye amaranth

The oxidation reaction of amaranth (trisodium 2-hydroxy-1-(4-sulfonato-1-naphthylazo)naphthalene-3,6-disulfonate or AM(-)) by chlorine dioxide (ClO(2)) in aqueous conditions was investigated in detail. The major reaction products immediately after decolorization of AM(-) were 1,2-naphthoquinone disulfonate sodium salt and 1,4-napthalenedione. The reaction had first-order dependence on both AM(-) and ClO(2). The rate-limiting step involved the reaction between AM(-) and OH(-) ions. The role of hydroxide ion as a catalyst was established. The second-order rate constant increased with pH, from (19.8 ± 0.9) M(-1) s(-1) at pH 7.0, (97.1 ± 2.3) M(-1) s(-1) at pH 8.0 to (132.5 ± 2.8) M(-1) s(-1) at pH 9.0. In the pH range of 6.0-7.5, the catalytic constant for OH(-) ion was 4.0 × 10(9) M(-2) s(-1). The energy and entropy of activation values for the reaction were 50.0 kJ mol(-1) and -658.7 J K(-1) mol(-1), respectively. A probable reaction mechanism was elucidated and was validated by simulations.     

Spectrophotometric determination of fluoxetine by batch and flow injection methods

A rapid, simple, and accurate spectrophotometric method is presented for the determination of fluoxetine by batch and flow injection analysis methods. The method is based on fluoxetine competitive complexation reaction with phenolphthalein-beta-cyclodextrin (PHP-beta-CD) inclusion complex. The increase in the absorbance of the solution at 554 nm by the addition of fluoxetine was measured. The formation constant for fluoxetin-beta-CD was calculated by non-linear least squares fitting. Fluoxetine can be determined in the range 7.0 x 10(-6)-2.4 x 10(-4) mol l(-1) and 5.0 x 10(-5)-1.0 x 10(-2) mol l(-1) by batch and flow methods, respectively. The limit of detection and limit of quantification were respectively 4.13 x 10(-6) mol l(-1) and 1.38 x 10(-5) mol l(-1) for batch and 2.46 x 10(-5) mol l(-1) and 8.22 x 10(-5) mol l(-1) for flow method. The sampling rate in flow injection analysis method was 80+/-5 samples h(-1). The method was applied to the determination of fluoxetine in pharmaceutical formulations and after addition to human urine samples.     

Hydrolysis Reactions and Resolution of (±)-2-Acetamido-3-hydroxy-1-(4-nitrophenyl)-1-propanone

IntroductionChloramphenicol,which was isolated fromStreptomyces venezuelae in 1 947[1] ,is used as abroad- spectrum antibiotic possessing activityagainst many Gram- negative and Gram- positivemicroorganisms. (± ) - 2 - Acetamido- 3 - hydroxy- 1 -(4- nitrophenyl) - 1 - propanone[(± ) - 1 ]is one of theintermediates of producing chloramphenicol.Petrow et al.[2 ] reported some transformations of(± ) - 1 in hydrolysis reactions. However,thereaction products were complicated under multiplehydr…     

Catalytic spectrofluorimetric determination of superoxide anion radical and superoxide dismutase activity using N,N-dimethylaniline as the substrate for horseradish peroxidase (HRP)

The coupled reaction of N,N-dimethylaniline (DMA) with 4-aminoantipyrine (4-AAP) using superoxide anion radical (O2-) as oxidizing agent under the catalysis of horseradish peroxidase (HRP) was studied. Based on the reaction, O2- produced by irradiating Vitamin B2, (VB2) was spectrophotometricly determined at 554 nm. The linear range of this method was 1.8 x 10(-6)-1.2 x 10(-4) mol l(-1) with a detection limit of 5.3 x 10(-7) mol l(-1). The effect of interferences on the determination of O2- was investigated. The proposed method was successfully applied to the determination of superoxide dismutase (SOD) activity in human blood and mouse blood.     

2 - 芳基 -4- 苯基 -2, 3- 二氢 -1, 5- 苯并二氮杂卓与重氮乙酸乙酯反应机 理和 立体化学的研究

2-芳基-4-苯基-2,3-二氢-1,5-苯并二氮杂卓与重氮乙酸乙酯在铜粉催化下反应,得到环加成产物吖丙啶并苯并二氮杂卓I外,还得到一个非预期的五员环产物吡咯并苯并二氮杂卓II。改变反应条件可以使化合物II的收率达到50%。通过研究反应过程中分离出的副产物反丁烯酸二乙酯III和4,5-二氢吡唑-3,4,5-三羧酸乙酯IV,初步提出了反应经过乙氧羰基甲基化苯并二氮杂卓翁中间体V再发生环加成反应的机制。通过X-射线单晶衍射分析和NMR分析研究了它们的立体化学,发现为立体专一性反应。     

Electrochemical, microscopic and spectroscopic characterization of benzene diamine functionalized single walled carbon nanotube-cobalt (II) tetracarboxy-phthalocyanine conjugates

In this paper we report on the synthesis and characterization of 1,4-benzene diamine (BDA) functionalized single walled carbon nanotubes linked to cobalt (II) tetracarboxy-phthalocyanine. The characterization of the conjugate was through UV-vis, FTIR and X-ray diffraction (XRD) spectroscopies and by transmission electron microscope (TEM) and electrochemical methods. The conjugate is used for the electrochemical characterization of diuron. The catalytic rate constant for diuron was 4.4×10(3)M(-1)s(-1) and the apparent electron transfer rate constant was 18.5×10(-6)cms(-1). The linear dynamic range was 1.0×10(-5)-2.0×10(-4)M, with a sensitivity of ～0.42Amol(-1)Lcm(-2) and a limit of detection of 0.18μM using the 3δ notation.