Optimization of synthesis process of photosensitizer chlorin f
-
摘要: 目的 改进光敏剂二氢卟吩f(1)的制备工艺。 方法 采用"一锅法",以脱镁叶绿酸a(3)为原料,在氢氧化钾醇液中通O2使E环氧化开裂后直接回流降解,制得化合物1。选择氧化开环反应时间、醇的种类、碱浓度及回流反应时间为影响1合成产率的4个主要考察因素,每个因素各取3个水平,采用正交试验设计优化制备1的反应条件。 结果 3粗品经10倍质量的25%氢氧化钾乙醇液于0℃下通O2反应30 min后,迅速通N2回流反应20 min,最终经硅胶H柱色谱分离制得1,产率达40.8%。 结论 该工艺具有操作安全、简便、收率高等优点。Abstract: Objective To improve the synthesis process of chlorine f(1). Methods A "one-pot" method was applied to prepare Photosensitizer component(1), using pheophorbide a(3) as raw material by oxidating and cracking of the E-ring of(3) with bubbling oxygen in alcoholic solution of potassium hydroxide at 0℃ followed by refluxing in nitrogen atmosphere. In order to obtain the optimal synthetic procedure, the orthogonal experimental design of L9(34) was adopted to investigate three different levels of four main factors i.e. ring opening reaction time, alcoholic variety, alkali concentration and refluxing reaction time. Results The target compound(1) was optimizedly synthesized through treatment of raw material(3) with bubbling oxygen in 25% ethanol solution of potassium hydroxide at 0℃ for 30 min, followed by refluxing in nitrogen atmosphere for 20 min in yield of 40.8%. Conclusion The procedure developed has some advantages of simple and safty operation, and high synthetic yield.
-
Key words:
- photosensitizer /
- chlorin f /
- orthogonal experimental design /
- process improvement
-
[1] Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer:an update[J]. CA Cancer J Clin, 2011, 61(4):250-281. [2] Kamkaew A, Lim SH, Lee HB, et al. BODIPY dyes in photodynamic therapy[J]. Chem Soc Rev, 2013, 42(1):77-88. [3] Oliveira KT, Momo PB, Assis FF, et al. Chlorins:natural sources, synthetic developments and main applications[J]. Current Organic Synthesis, 2014, 11(1):42-58. [4] Zhang JL, Deng L, Yao JZ, et al. Synthesis and photobiological study of a novel chlorin photosensitizer BCPD-18MA for photodynamic therapy[J]. Bioorg Med Chem, 2011, 19(18):5520-5528. [5] 姚建忠,贺祥,沈卫镝,等. 二氢卟吩f的合成及肿瘤光生物活性[J]. 中国药学杂志, 1999, 34(12):846-848. [6] 姚建忠,陈文辉,贺祥,等. 二氢卟吩F甲醚的合成及其光敏化力和肿瘤光生物活性[J]. 药学学报,2000, 35(1):63-66. [7] 姚建忠,沈卫镝,刘建飞,等. 2-(1-羟基)乙基二氢卟吩f及其醚衍生物对小鼠肉瘤180移植瘤的光化学治疗作用[J]. 中国激光医学杂志,2000, 9(4):228-230. [8] 姚建忠,刘建飞,张万年,等. 2-(1-羟基)乙基二氢卟吩f及其醚衍生物的合成和肿瘤光生物活性[J]. 中国药物化学杂志,2001, 11(1):1-4. [9] 姚建忠,张万年,王小燕,等. 正交实验设计优化二氢卟吩f的制备反应条件[J]. 数理医药学杂志,2002, 15(4):361-362. [10] 周怀梧. 医药用数理统计[M].济南:山东教育出版社,1986:148. [11] 马志庆,周介南. 医药数理统计.4版.[M]. 北京:科学出版社,2012:174-177. -
点击查看大图
计量
- 文章访问数: 3387
- HTML全文浏览量: 405
- PDF下载量: 22
- 被引次数: 0
下载:
