Divergence en route to nonclassical annonaceous acetogenins. Synthesis of pyranicin and pyragonicin

Syntheses of the nonclassical annonaceous acetogenins, pyranicin, and pyragonicin from common late-stage intermediates are presented. The construction of key elements relies on asymmetric HWE reactions, including the desymmetrization of a meso-dialdehyde and a parallel kinetic resolution of a racemic aldehyde. A stereoconvergent Pd-catalyzed substitution serves to install the C4 stereocenter in protected form with different orthogonal protective groups. A divergent strategy to form 1,4- and 1,6-diols, employing stereoselective Zn-mediated alkynylations, is used for completion of the core structures. Notably, the stereoselective coupling reaction toward pyragonicin proceeds with highly functionalized fragments. The methodology is further expanded by a divergent synthesis of all stereoisomers of the 2,3,6-trisubstituted tetrahydropyran subunit.     

Synthesis of pyragonicin

[structure: see text] A stereocontrolled convergent synthesis of the annonaceous acetogenin pyragonicin (1) is presented. The key intermediates were accessed using asymmetric Horner-Wadsworth-Emmons (HWE) methodology. A reagent controlled zinc-mediated stereoselective coupling, joining the two highly functionalized intermediates 3 and 4, then provided the core structure.     

Convergent synthesis of pyragonicin

This paper describes a second-generation synthesis of an antitumor tetrahydropyran (THP) acetogenin, pyragonicin. The key step involved an olefin cross-metathesis between the THP segment and the terminal gamma-lactone residue. The coupling reaction in the presence of Grubbs' second-generation catalyst resulted in an unseparable mixture of a desired coupling product and its one-carbon eliminated product while the use of Grubbs' first-generation catalyst afforded the former exclusively. A novel MOM-migrating reaction found in a cyclization reaction is also discussed.     

SmI2‐induced cyclizations and their applications in natural product synthesis

Since the isolation of brevetoxin‐B, a red tide toxin, many bioactive marine natural products featuring synthetically challenging trans‐fused polycyclic ether ring systems have been reported. We have developed SmI₂‐induced cyclization of β‐alkoxyacrylate with aldehyde, affording 2,6‐syn‐2,3‐trans‐tetrahydropyran (THP) or 2,7‐syn‐2,3‐trans‐oxepane with complete stereoselection, as a key reaction of efficient iterative and bi‐directional strategies for the construction of these polycyclic ethers. This reaction is also applicable to the synthesis of 3‐, 5‐, and 6‐methyl‐THPs and 3,5‐dimethyl‐THP. The synthesis of 2‐methyl‐ and 2,6‐dimethyl‐THPs was accomplished by means of a unique methyl insertion. Recently, the SmI₂‐induced cyclization was extended to similar reactions using β‐alkoxyvinyl sulfone and sulfoxide. Reaction of (E)‐ and (Z)‐β‐alkoxyvinyl sulfone‐aldehyde afforded 2,6‐syn‐2,3‐trans‐ and 2,6‐syn‐2,3‐cis‐ THPs, respectively. Reaction of (E)‐β‐alkoxyvinyl (R)‐ and (S)‐sulfoxides gave 2,6‐anti‐2,3‐cis‐ and 2,6‐syn‐2,3‐trans‐THPs, respectively. Reaction of (Z)‐β‐alkoxyvinyl (R)‐sulfoxides gave 2,6‐syn‐2,3‐cis‐THP and an olefinic product, while that of (Z)‐β‐alkoxyvinyl (S)‐sulfoxide afforded a mixture of many products. These SmI₂‐induced cyclizations have been applied to the total syntheses of various natural products, including brevetoxin‐B, mucocin, pyranicin, and pyragonicin. Synthetic studies on gambierol and maitotoxin are also introduced. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 159–172; 2010: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.200900027     

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.     

Conversion of bis(trichloromethyl) carbonate to phosgene and reactivity of triphosgene, diphosgene, and phosgene with methanol(1)

Triphosgene was decomposed quantitatively to phosgene by chloride ion. The reaction course was monitored by IR spectroscopy (React-IR), showing that diphosgene was an intermediate. The methanolysis of triphosgene in deuterated chloroform, monitored by proton NMR spectroscopy, gave methyl chloroformate and methyl 1,1, 1-trichloromethyl carbonate in about a 1:1 ratio, as primary products. The reaction carried out in the presence of large excess of methanol (0.3 M, 30 equiv) was a pseudo-first-order process with a k(obs) of 1.0 x 10(-)(4) s(-)(1). Under the same conditions, values of k(obs) of 0.9 x 10(-)(3) s(-)(1) and 1.7 x 10(-)(2) s(-)(1) for the methanolysis of diphosgene and phosgene, respectively, were determined. The experimental data suggest that, under these conditions, the maximum concentration of phosgene during the methanolysis of triphosgene and diphosgene was lower than 1 x 10(-)(5) M. Methyl 1,1,1-trichloromethyl carbonate was synthesized and characterized also by the APCI-MS technique.     

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.     

用银-色氨酸复合膜修饰玻碳电极循环伏安法测定去甲肾上腺素

在含有1.0mmol.L-1硝酸银、5.58×10-2 mol.L-1色氨酸的溶液中,于-0.8～1.8V(vs.Ag/AgCl)电位下,在玻碳电极表面电沉积一层银-色氨酸复合膜,制得银-色氨酸复合膜修饰玻碳电极(Ag-TRY/GCE)。采用扫描电镜对电极表面的性能进行表征,循环伏安法对其电化学性能进行研究。试验发现:在pH 6.0磷酸盐缓冲溶液中,去甲肾上腺素(NE)在修饰电极出现一对明显的氧化还原峰,氧化峰电位为0.306V,还原峰电位为0.368V,提出了用循环伏安法测定NE的方法。在试验条件下,氧化峰电流与去甲肾上腺素浓度在3.4×10-7～8.3×10-6 mol.L-1和8.3×10-6～1.1×10-4 mol.L-1两段范围内呈线性关系,检出限(3S/N)为4.3×10-8 mol.L-1。修饰电极用于药物中去甲肾上腺素的测定,加标回收率在95.6%～99.4%之间。     

两种四乙酸四氮杂环烷化合物的合成

在氢氧化钾存在下，1，4，7，10-四氮杂环十二烷与溴乙酸进行N-羧甲基化反应，得到N，N′N″N-四乙酸1，4，7，10-四氛杂环十二烷（DOTA，I），经重结晶纯化，产率88．1％．在碳酸钾存在下，1，4，8，11-四氮杂环十四烷与溴乙酸卡酯进行反应，生成N－乙酸苄酯中间体．该中间体在室温和4．04×105Pa氢气压力下，用Pd／C地催化氢解脱苄基得到N，N′N″N-四乙酸1，4，8，11－四氮杂环十四烷（TETA，Ⅲ），产率56．0％。     

聚合物试剂的研究——Ⅱ.应用聚合物试剂合成桃柱螟性信息素——反-10-十六碳烯-1-醛

以二甲亚砜钠盐和四氢呋喃作为碱和溶剂,应用聚合物 Wittig 试剂合成顺-10-十六碳烯-1-醇5,产率31%,选择性可达90%。5经异构化得反式-10-十六碳烯-1-醇6,6的异构体比例达到生物活性要求。6氧化后得到桃柱螟性信息素——反-10-十六碳烯-1-醛7。产物结构均经 IR、NMR、MS 和元素分析等得到证实。     

Spectrofluorimetric study on the inclusion interaction between vitamin K3 with p-(p-sulfonated benzeneazo)calix[6]arene and determination of VK3

The characteristics of host-guest complexation between p-(p-sulfonated benzeneazo) calix[6]arene (SBC6A) and vitamin K3 (VK3) were investigated by fluorescence spectrometry. A 1:1 stoichiometry for the complexation was established and was verified by Job's plot. An association constant of 4.95 x 10(3)L mol(-1) at 20 degrees C was calculated by applying a deduced equation. The interaction mechanism of the inclusion complex was discussed. It was found that the fluorescence of SBC6A could be remarkably quenched by an appropriate amount of VK3 especially when non-ionic surfactant Triton X-100 existed. According to the obtained results, a novel sensitive spectrofluorimetric method for the determination of VK3 based on supramolecular complex was developed with a linear range of 5.0 x 10(-7) -3.0 x 10(-5)mol L(-1) and a detection limit of 2.0 x 10(-7)mol L(-1). The proposed method was used to determine VK3 in commercial preparations with satisfactory results.     

A New Technique of Synthesizing 10—Hydroxy—5—methyl—5,10—dihydrophenophosphazine 10—Oxide

10-Hydroxy-5-methyl-5,10-dihydrophenophosphazine 10-oxide(1)was prepared by a new technique of treating 10-methoxy-5,10-dihydrophenophosphazine 10-oxide(2)with an equivalent of NaH in anhydrous DMF,and then at 120℃ for 3-4h,which not only avoided poisonous and expensive methyl iodide used in literature,but made the consumption of NaH greatly decrease as well.The possible reaction mechanism was also described.The chemical structure of 1 was confiremed by IR,NMR,and mass spectroscopy.     

基于拮抗作用检测除草剂的类囊体膜生物传感器研究

利用除草剂对植物类囊体束缚酶分解过氧化氢的拮抗作用,研制了一种快速检测痕量除草剂的电化学生物传感器.将植物类囊体用聚乙烯醇-苯乙烯吡啶(PVA-SbQ)光敏聚合剂在紫外光诱导下产生大分子网状结构进行包埋,制成生物敏感膜,并固定在铂电极表面.根据加入除草剂时类囊体膜束缚酶分解过氧化氢活性的变化,对除草剂进行测定.在含有1×10^-3mol/LNaCl,5×10^-3mol/LMgCl₂和0.01mol/LH₂O₂的Tris-HCl缓冲溶液(pH=7.4)中,基于测量0.65V处H₂O₂氧化电流的变化,可以对下列浓度的除草剂进行定量检测:百草枯3×10^-9～1.5×10^-7mol/L,敌草龙1×10^-8～3×10^-7mol/L,扑草净4×10^-8～3×10^-6mol/L,阿特拉津1×10^-7～5×10^-6mol/L,莠灭净1×10^-7～5×10^-6mol/L.利用PVA-SbQ光聚合膜固定类囊体,能够使酶的活性在低温下保持数月.     

生物素-亲和素体系测定雌酮

雌酮与牛血清白蛋白共价结合,合成雌酮的完全抗原。利用此抗原免疫小鼠,通过细胞融合技术制备了雌酮的单克隆抗体,经纯化表征知,抗体是IgG1型,相对分子量为164000,与固定抗的亲和常数为8.2×10^8L/mol。以生物素化的羊抗鼠免疫球蛋白及辣根过氧化物酶标记的链亲和素为标记体系,通过竞争抑制的方式测定游离的雌酮,结果表明：雌酮在10～10000pg/mL内呈线性关系。     

碳纳米管负载氢氧化镍修饰电极的制备及应用

采用表面滴涂结合循环伏安法制备了碳纳米管负载氢氧化镍修饰电极(Ni(OH)2/MWNT/CCE)。研究了该修饰电极对葡萄糖的电催化氧化性能。结果表明,该修饰电极对葡萄糖具有良好的电催化氧化活性。在优化条件下,安培法检测葡萄糖的线性范围为2.0×10-7～5.7×10-4 mol.L-1(r=0.999 9,s=2 786.5μA.(mmol.L-1)-1.cm-2)和5.7×10-4～2.7×10-3 mol.L-1(r=0.999 1,s=2 005.2μA.(mmol.L-1)-1.cm-2),检出限(3sb)为8.0×10-8 mol.L-1。该法已成功用于血清中葡萄糖含量的测定。     

Determination of secnidazole in urine by adsorptive stripping voltammetry

Cyclic voltammetry was used to explore the adsorption behavior of secnidazole on a hanging mercury drop electrode (HMDE). The effects of various operational parameters on the accumulation behavior of the adsorbed species were tested. Thus, a sensitive stripping voltammetry procedure for the determination of secnidazole with an adsorptive accumulation on the surface of HMDE has been developed. Measurements were taken by differential-pulse voltammetry after determination of the optimum conditions. The linear concentration range was 1 x 10(-8)-1 x 10(-7) s when using a 120 s preconcentration at -0.1 V vs. Ag/AgCl in acetate buffer of pH 4.0. The detection limit of secnidazole was 5 x 10(-9) M. The precision, expressed by the coefficient of variation, was 2.5% (n = 10) at a concentration of 1 x 10(-7) m. The method was successfully applied to the analysis of secnidazole in urine.     

(10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: an improved synthesis via 19-nor-10-oxo-vitamin D

An efficient synthetic route to (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3 was developed. The key feature of this pathway is the introduction of a 19-fluoromethylene group to a (5E)-19-nor-10-oxo-vitamin D derivative. The 10-oxo-compound was obtained via a 1,3-dipolar cycloaddition reaction of (5E)-1alpha,25-dihydroxyvitamin D with in situ generated nitrile oxide followed by ring cleavage of the formed isoxazoline moiety with molybdenum hexacarbonyl. Conversion of the keto group of (5E)-19-nor-10-oxo-vitamin D to the E and Z fluoromethylene group was achieved through a two-step sequence involving a reaction of lithiofluoromethyl phenyl sulfone followed by the reductive desulfonylation of the alpha-fluoro-beta-hydroxy sulfone. The dye-sensitized photoisomerization of the (5E)-19-fluorovitamin D afforded the desired (5Z)-19-fluorovitamin D derivatives, (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3.     

流动注射化学发光法测定槐米中槲皮素

在碱性溶液中槲皮素对过氧化氢氧化鲁米诺而产生的化学发光(CL)具有很强的抑制作用,且其CL强度的减弱程度与槲皮素浓度之间在一定的范围内呈线性关系。据此,并结合应用流动注射(FI)技术,提出了FI-CL测定槐米中槲皮素含量的方法。反应体系中所用试剂的最佳浓度为:①cH2O2=0.2mol.L-1;②c鲁米诺=8.5×10-4mol.L-1;③cNaOH=0.01mol.L-1。对槲皮素测定的线性范围为2.65×10-6～5.31×10-4mol.L-1之间,其检出限(3s/k)为9.26×10-7mol.L-1。用4×10-4mol.L-1槲皮素标准溶液进行精密度试验,测得相对标准偏差(n=11)为3.0%。分析试样时,先从槐米在pH 8～9的碱性溶液中提取芦丁,然后在微酸性(pH 5)溶液中使芦丁水解得到槲皮素粗品。将此粗品经反复重结晶得到槲皮素纯品,溶于乙醇(40+60)溶液中制成溶液,用于FI-CL分析。     

Organic-inorganic composite cation-exchanger: poly-o-toluidine Zr(IV) phosphate-based ion-selective membrane electrode for the potentiometric determination of mercury

A new heterogeneous precipitate of an organic-inorganic composite cation-exchanger poly-o-toluidine Zr(IV) phosphate was utilized for the preparation of a Hg(II) ion-sensitive membrane electrode for the determination of Hg(II) ions in real aqueous as well as in real samples. The electrode showed good potentiometric response characteristics, and displayed a linear log[Hg(2+)] versus EMF response over a wide concentration range of 1 x 10(-1) - 1 x 10(-6) M with a Nernstian slope of 30 mV per decade change in concentration with a detection limit of 1 x 10(-6). The membrane electrode showed a very fast response time of 5 s and could be operated well in the pH range 2 - 8. The selectivity coefficients were determined by the mixed-solution method, and revealed that the electrode was selective in the presence of interfering cations; however most of these did not show significant interference in the concentration range of 1 x 10(-1) - 1 x 10(-4) M. The lifetime of the membrane electrode was observed to be 120 days. The analytical utility of this electrode was established by employing it as an indicator electrode in the potentiometric titrations of Hg(2+) ions from a synthetic mixture as well as drain water.     

Synthesis and bioassay of all four stereoisomers of (2E,4E)-4,6,10,12-tetramethyl-2,4-tridecadien-7-one, the assignment of the absolute configuration of the sex pheromone of Matsucoccus matsumurae Japanese pine bast scale

A facile enantioselective synthesis of all four stereoisomers of (2E,4E)-4,6,10,12-tetramethyl-2,4-tridecadien-7-one (1) is described. The stereochemistry at 6-C and 10-C of 1 was constructed by using optically active citronellal as starting material and by the asymmetric crotylic metal reaction. In the bioassay and field tests, only la, i.e. (6R,10R)-1 was active. The other three isomers 1b (6S,10R), 1c (6R,10S) and 1d (6S,10S) were inactive. Therefore, the naturally occurring pheromone was assigned as (6K,10R)-1.