有机化学 ›› 2012, Vol. 32 ›› Issue (04): 742-746.DOI: 10.6023/cjoc1109263 上一篇    下一篇

研究论文

二茂铁-肽缀合物CH3O-Fc-NH-ΔPhe-COPh 的合成及性质研究

潘成学, 王忠长, 苏桂发, 宗玺, 薛文彬, 覃江克   

  1. 广西师范大学化学化工学院 药用资源化学与药物分子工程国家重点实验室培育基地 桂林 541004
  • 收稿日期:2011-09-26 修回日期:2011-11-11 出版日期:2012-04-25 发布日期:2012-04-24
  • 通讯作者: 苏桂发 E-mail:edward_su75@163.com
  • 基金资助:

    国家自然科学基金(No. 20862003)、广西自然科学基金创新团队(No. 2010GXNSFF013001)资助项目.

Synthesis, Structure and Properties of Ferrocene-Peptide Conjugates CH3O-Fc-NH-ΔPhe-COPh

Pan Chengxue, Wang Zhongchang, Su Guifa, Zong Xi, Xue Wenbin, Qin Jiangke   

  1. State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, College of Chemistry & Chemical Engineering, Guangxi Normal University, Guilin 541004
  • Received:2011-09-26 Revised:2011-11-11 Online:2012-04-25 Published:2012-04-24
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 20862003), and the Natural Science Foundation Innovative Team of Guangxi Province of China (No. 2010GXNSFF013001).

以二茂铁二甲酸为原料, 经酯化、部分水解、与叠氮化钠反应、在叔丁醇中发生Curtius 重排得到1'-甲酸甲酯-1-叔丁氧胺基二茂铁(5), 5 经三氟乙酸脱保护、与(Z)-2-苯基-4-苯甲基噁唑-5-酮反应, 合成了含α,β-不饱和氨基酸残基的二茂铁-肽缀合物CH3O-Fc-NH-ΔPhe-COPh (7) (ΔPhe 为α,β-不饱和苯丙氨酸). 用红外、核磁、质谱和元素分析对其结构进行鉴定和表征. 用循环伏安(CV)法对产物的电化学性能进行研究, 结果表明化合物7 的氧化峰和还原峰的电位分别为0.802 和0.714 V, 峰电位之差ΔEp 为88 mV, 峰电流密度之比Jpa/Jpc 为1.06. 用荧光光谱研究了近生理条件下化合物7 与牛血清白蛋白(BSA)的相互作用, 结果表明化合物7 与BSA 间的相互作用为静态猝灭过程, 反应结合位点数为0.93, 结合常数为3.8×104 L?mol-1.

关键词: 二茂铁-肽缀合物, 合成, α,β-不饱和氨基酸, 循环伏安法, 荧光性质

Methyl 1'-Boc-aminoferrocene-1-carboxylate (5) was synthesized from 1,1'-ferrocenedicarboxylic acid, via esterification, partially hydrolysis, reaction with sodium azide and Curtius rearrangement. The Boc protection of 5 was removed with trifluoroacetic acid (TFA), then reacted with 4-benzylidene-2-phenyl-4H-oxazol-5-one to afford a novel ferrocene-petide conjugate CH3O-Fc-NH-ΔPhe-COPh (7) with α,β-unsaturated acid residue. The compound was characterized by IR, NMR, MS and elemental analyses. Its electrochemical behavior was tested by cyclic voltammetry (CV). The results showed that the title compound exhibits a pair of well-defined redox wave at oxidation potential (Ea) and reduction potential (Ec) of CH3O-Fc-NH-ΔPhe-COPh at 0.802 and 0.714 V, respectively, in the range of 0.4~1.1 V; and the ratio of Jpa/Jpc is 1.06. Under the simulated physiological conditions, the interaction between compound 7 and bovine serum albumin (BSA) was investigated by fluorescence spectrum. Results indicated that the combination reaction of them was a single static quenching process and with a conformational change of BSA. The number of binding site n and equilibrium (binding) constant were 0.93 and 3.8×104 L?mol-1, respectively.

Key words: ferrocene peptides, synthesis, α,β-unsaturated acids, cyclic voltammetry, fluorescence spectrum