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正交实验设计优化光敏剂紫红素-18的合成工艺
引用本文:王曜,姚建忠,缪震元,盛春泉,张万年. 正交实验设计优化光敏剂紫红素-18的合成工艺[J]. 药学实践杂志, 2011, 29(2): 114-116
作者姓名:王曜  姚建忠  缪震元  盛春泉  张万年
作者单位:第二军医大学药学院,上海,200433
基金项目:国家自然科学基金(30371737)和上海市重点学科建设基金(B906)资助项目.
摘    要:
目的优化光敏剂紫红素-18(1)的合成工艺。方法以脱镁叶绿酸a(2)为原料,经空气氧化及碱开环制得化合物1;选择影响其合成产率的反应时间(A)、氢氧化钾溶液浓度(B)、反应溶剂(C)和化合物2与氢氧化钾的质量投料比(D)为考察因素,每个因素各取三个水平,采用L9(34)正交试验法优化目标物1的最佳合成工艺。结果合成目标物1的最优反应条件为B1C2A2D2,反应工艺收率从34.4%提高到45.6%。结论新工艺提高了收率、缩短了反应时间、消除了毒性溶剂,适合工业化生产

关 键 词:药物化学  工艺改进  紫红素-18  正交设计  光敏剂
收稿时间:2010-06-17
修稿时间:2010-11-01

Optimization of the synthesis of photosensitizer purpurin-18 by orthogonal design
WANG Yao,YAO Jian-zhong,MIAO Zhen-yuan,SHENG Chun-quan and ZHANG Wan-nian. Optimization of the synthesis of photosensitizer purpurin-18 by orthogonal design[J]. The Journal of Pharmaceutical Practice, 2011, 29(2): 114-116
Authors:WANG Yao  YAO Jian-zhong  MIAO Zhen-yuan  SHENG Chun-quan  ZHANG Wan-nian
Affiliation:School of Pharmacy, The Second Military Medical University, Shanghai 200433, China;School of Pharmacy, The Second Military Medical University, Shanghai 200433, China;School of Pharmacy, The Second Military Medical University, Shanghai 200433, China;School of Pharmacy, The Second Military Medical University, Shanghai 200433, China;School of Pharmacy, The Second Military Medical University, Shanghai 200433, China
Abstract:
Objective To optimize the synthesis of photosensitizer purpurin-18(1). Methods Target compound 1 was synthesized through air oxidation and simultaneously ring cleavage of pheophorbide a (2) in presence of alkali. Four main factors influencing synthetic yield of 1 such as reaction time (A), concentration of potassium hydroxide (B), solvent (C) and weight ratio of material 2 to potassium hydroxide (D),which was chosed three levels respectively,were evaluated by the orthogonal experimental design of L9 (34). Results The optimization term of the synthesis of target compound 1 was B1C2A2D2. The yield of 1 was raised from 34.4% to 45.6%. Conclusion The yield was raised. The reaction time was shortened and the toxic solvent was removed. The procedure was suitable for industrial production.
Keywords:medicinal chemistry  process improvement  purpurin-18  orthogonal design  photosensitizer
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