5-取代-3,4-二卤-2(5H)-呋喃酮的Sonogashira偶联反应

以5-取代-3,4-二卤-2(5H)-呋喃酮为底物进行Sonogashira偶联反应, 考察了反应温度、反应时间、钯催化剂种类与用量、碱种类与用量、溶剂、底物结构等对偶联反应的影响, 合成了28种新的2(5H)-呋喃酮衍生物, 其结构用IR, ¹H NMR, ¹³C NMR, MS和元素分析等方法进行了表征. 在优化的反应条件下, 即反应溶剂为甲苯、催化剂为3 mol% Pd(PPh₃)₄和10 mol% CuI、碱为6 equiv. KF、反应时间72 h、反应温度30 ℃时, 反应产率42%～84%. 利用该Sonogashira偶联反应合成新型的多官能团烯二炔结构化合物, 不仅合成途径简捷、反应条件温和, 绝大部分反应产率中等以上, 而且无需额外加入配体, 适用于芳香的和脂肪的末端炔烃.     

分子模拟研究烯二炔环发色团分子从新制癌菌素的释放机理

烯二炔环发色团分子(Enediyne ring chromophore)虽然对DNA具有较好的切割性, 但由于它缺乏稳定性, 必须与蛋白结合形成非共价化合物(即新制癌菌素: Neocarzinostatin)才能进入细胞发挥生理作用. 作为一种已在临床上应用的抗肿瘤药物, 烯二炔环发色团分子从结合蛋白释放到细胞过程仍然是不清楚的. 以新制癌菌素复合物和对应的结合蛋白的X射线衍射结构作为研究对象, 运用分子动力学的模拟和拉伸动力学方法研究烯二炔环发色团分子从结合蛋白中释放的机理. 模拟结果表明从萘酸基方向释放可能是烯二炔环发色团分子最佳的释放路径.     

Reactivity of Bispropargyl Sulfones under Basic Conditions: Interplay Between Garratt–Braverman and Schmittel/Myers–Saito Cyclization Pathway

The preference for Garratt–Braverman (GB) over Myers–Saito (MS) and Schmittel (SCM) cyclizations has recently been demonstrated in sulfones capable of undergoing all three of the processes. As the GB cyclization is a self-quenching process, there is a need to change the selectivity to the non-self-quenching MS or SCM pathway so as to enhance the DNA-cleaving efficiency that operates through the radical-mediated process. Herein we report a conformational constraint-based strategy developed by using computations (M06-2X/6-31+G*) to switch the selectivity from GB to MS/SCM pathway which also results in greater DNA-cleavage activity. The preference for GB could be brought back by easing the constraint with the help of spacers.     

Synthesis of Chlorin—enediyne Dyads by Palladium—catalyzed Coupling Reaction

Methyl 9-ethylenedioxpyropheophorbide-d was prepared from methyl pyropheophorbide-a by protection of cyclic ketone with ethylene glycol,and oxidation with OsO4 in vinyl group at 2-position.The terminal alkyne was introduced into chlorin chromophore by Grignard reaction,and the enediyne moiety was constructed by a palladium-catalyzed coupling reaction with (Z)-chloroenynes.     

The Bergman cyclizations of the enediyne and its N-substituted analogs using multiconfigurational second-order perturbation theory

The Bergman cyclizations of the enediyne and its four N-substituted analogs [(Z)-pent-2-en-4-ynenitrile, 3-azahex-3-en-1,5-diyne, malenotrile, and 3,4-azahex-3-en-1,5-diyne] have been studied using the complete active space self-consistent field and multiconfigurational second-order perturbation theory methods in conjunction with the atomic natural orbital basis sets. The geometries and energies of the reactants, transition states, and products along both the S₀ (the ground state) and T₁ (the lowest-lying triplet state) potential energy surfaces (PESs) were calculated. The calculated geometries are in good agreement with the available experimental data. The distance between two terminal carbons in enediyne, which was considered as an important parameter governing the Bergman cyclization, was predicted to be 4.319 Å, in agreement with the experimental value of 4.321 Å. Our calculations indicate that the replacements of the terminal C atom(s) or the middle C atom(s) in the CC bond by the N atom(s) increase or decrease the energy barrier values, respectively. There exist stable ring biradical products on the T₁ PESs for the five reactions. However, on the S₀ PESs the ring biradical products exist only for the reactions of enediyne, (Z)-pent-2-en-4-ynenitrile, and 3-azahex-3-en-1,5-diyne. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011