正交设计优化光敏剂二氢卟吩e<sub>6</sub>-C<sub>15</sub>单甲酯的合成工艺

单彬; 孙渺; 孟志; 韩贵焱; 钱其涵; 刘明辉; 姚建忠

doi:10.3969/j.issn.1006-0111.2015.02.007

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正交设计优化光敏剂二氢卟吩e₆-C₁₅单甲酯的合成工艺

单彬, 孙渺, 孟志, 韩贵焱, 钱其涵, 刘明辉, 姚建忠

文章导航 > 药学实践与服务 > 2015 > 33(2): 122-124

单彬, 孙渺, 孟志, 韩贵焱, 钱其涵, 刘明辉, 姚建忠. 正交设计优化光敏剂二氢卟吩e6-C15单甲酯的合成工艺[J]. 药学实践与服务, 2015, 33(2): 122-124. doi: 10.3969/j.issn.1006-0111.2015.02.007

引用本文:

单彬, 孙渺, 孟志, 韩贵焱, 钱其涵, 刘明辉, 姚建忠. 正交设计优化光敏剂二氢卟吩e₆-C₁₅单甲酯的合成工艺[J]. 药学实践与服务, 2015, 33(2): 122-124. doi: 10.3969/j.issn.1006-0111.2015.02.007

SHAN Bin, SUN Miao, MENG Zhi, HAN Guiyan, QIAN Qihan, LIU Minghui, YAO Jianzhong. Optimization of synthesis of photosensitizer chlorin e6-C15 monomethyl ester by the orthogonal design[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 122-124. doi: 10.3969/j.issn.1006-0111.2015.02.007

Citation:

SHAN Bin, SUN Miao, MENG Zhi, HAN Guiyan, QIAN Qihan, LIU Minghui, YAO Jianzhong. Optimization of synthesis of photosensitizer chlorin e₆-C₁₅ monomethyl ester by the orthogonal design[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 122-124. doi: 10.3969/j.issn.1006-0111.2015.02.007

正交设计优化光敏剂二氢卟吩e₆-C₁₅单甲酯的合成工艺

doi: 10.3969/j.issn.1006-0111.2015.02.007

1.
福建中医药大学药学院, 福建福州 350108
2.
第二军医大学药学院, 上海 200433
3.
福建中医药大学药学院, 福建福州 350108;第二军医大学药学院, 上海 200433

基金项目: 国家自然科学基金(81172950);上海市科委重点科技攻关项目(11431920401)

Optimization of synthesis of photosensitizer chlorin e₆-C₁₅ monomethyl ester by the orthogonal design

1.
Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
2.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China
3.
Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

摘要: 目的优化光敏剂二氢卟吩e₆-C₁₅单甲酯 (1)的合成工艺。方法采用"一锅法", 以脱镁叶绿酸a 为原料, 通N₂条件下经碱甲醇液作用下E环开裂后直接添加1/20体积量的水, 回流水解制得化合物1。选择影响其合成产率的开环反应时间(A)、回流水解反应时间(B)、氢氧化钾甲醇液浓度(C)、3与氢氧化钾的质量投料比(D)为主要考察因素, 每个因素各取3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。结果合成化合物1的最优反应条件为B₁C₂A₂D₁, 工艺收率从43.0%提高到56.5%。结论该工艺具有操作简便、安全、收率高等优点, 适合工业化生产。
- 工艺改进 /
- 二氢卟吩e₆-C₁₅单甲酯 /
- 正交设计 /
- 光敏剂
Abstract: Objective To optimize the synthesis of photosensitizer chlorine e₆-C₁₅ monomethyl ester (1). Methods Target compound 1 was synthesized through E ring cracking of pheophorbide a (3) in methanol solution of potassium hydroxide followed by adding H₂O for ester hydrolysis with "one-pot" process. Four main factors that influencing the synthetic yield of target compound 1 are ring cleavage reaction time (A), reflux hydrolysis reaction time (B), alkali concentration (C) and weight ratio of material 3 to alkali (D). Each of the four factors was chosen at three levels and evaluated by the orthogonal experimental design of L₉(3⁴). Results The optimization terms of the synthesis of target compound 1 were B₁C₂A₂D₁. The yield of compound 1 was raised from 43.0% to 56.5%. Conclusion The developed process has the advantages of simple operation, good safety and high reaction yield, and is suitable for industrial production.
- process improvement /
- chlorine e₆-C₁₅ monomethyl ester /
- orthogonal design /
- photosensitizer

[1]	Juzeniene A, Moan J. The history of PDT in Norway Part one: identification of basic mechanisms of general PDT [J]. Photodiag Photodyn Ther, 2007, 4(1): 3-11.
[2]	Xu DY. Research and development of photodynamic therapy photosensitizers in China[J]. Photodiag Photodyn Ther, 2007, 4(1): 13-25.
[3]	Yao JZ, Zhang WN, Sheng CQ, et al. Design, synthesis, and in vitro photodynamic activities of benzochloroporphyrin derivatives as tumor photosensitizers [J]. Bioorg Med Chem Lett, 2008, 18(1): 293-297.
[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]	张丹萍,陈志龙,杨晓霞. 光动力药物的研究与开发[J]. 药学进展, 2007, 31(12): 529.
[6]	方瑛,许德余. 二氢卟吩e₆-C₁₅单甲酯:一种发展中的第二代光动力治癌新药候选化合物[J]. 中国激光医学杂志, 1999, 8(4): 235.
[7]	方瑛,许德余. 蚕沙叶绿素的降解及二氢卟吩e₆醚类衍生物的合成[J]. 有机化学,1995, 15(5): 493.
[8]	姚建忠,许德余,陈文晖,等. 蚕沙叶绿素的降解及二氢卟吩P₆酰胺衍生物的合成[J].中国医药工业杂志,1999, 30(9): 403.
[9]	周怀梧. 医药用数理统计[M]. 济南:山东教育出版社,1986:148.
[10]	张春华,严云良. 医药用数理统计[M]. 北京:科学出版社,2001:205.

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正交设计优化光敏剂二氢卟吩e₆-C₁₅单甲酯的合成工艺

doi: 10.3969/j.issn.1006-0111.2015.02.007

1. 福建中医药大学药学院, 福建福州 350108

2. 第二军医大学药学院, 上海 200433

3. 福建中医药大学药学院, 福建福州 350108;第二军医大学药学院, 上海 200433

基金项目: 国家自然科学基金(81172950);上海市科委重点科技攻关项目(11431920401)

收稿日期: 2014-08-26
修回日期: 2014-11-17

关键词:

工艺改进 /

二氢卟吩e₆-C₁₅单甲酯 /

正交设计 /

光敏剂

摘要: 目的优化光敏剂二氢卟吩e₆-C₁₅单甲酯 (1)的合成工艺。方法采用"一锅法", 以脱镁叶绿酸a 为原料, 通N₂条件下经碱甲醇液作用下E环开裂后直接添加1/20体积量的水, 回流水解制得化合物1。选择影响其合成产率的开环反应时间(A)、回流水解反应时间(B)、氢氧化钾甲醇液浓度(C)、3与氢氧化钾的质量投料比(D)为主要考察因素, 每个因素各取3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。结果合成化合物1的最优反应条件为B₁C₂A₂D₁, 工艺收率从43.0%提高到56.5%。结论该工艺具有操作简便、安全、收率高等优点, 适合工业化生产。

English Abstract

Optimization of synthesis of photosensitizer chlorin e₆-C₁₅ monomethyl ester by the orthogonal design

1. Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China

2. School of Pharmacy, Second Military Medical University, Shanghai 200433, China

3. Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2014-08-26
Rev Recd Date: 2014-11-17

Keywords:

Abstract: Objective To optimize the synthesis of photosensitizer chlorine e₆-C₁₅ monomethyl ester (1). Methods Target compound 1 was synthesized through E ring cracking of pheophorbide a (3) in methanol solution of potassium hydroxide followed by adding H₂O for ester hydrolysis with "one-pot" process. Four main factors that influencing the synthetic yield of target compound 1 are ring cleavage reaction time (A), reflux hydrolysis reaction time (B), alkali concentration (C) and weight ratio of material 3 to alkali (D). Each of the four factors was chosen at three levels and evaluated by the orthogonal experimental design of L₉(3⁴). Results The optimization terms of the synthesis of target compound 1 were B₁C₂A₂D₁. The yield of compound 1 was raised from 43.0% to 56.5%. Conclusion The developed process has the advantages of simple operation, good safety and high reaction yield, and is suitable for industrial production.

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正交设计优化光敏剂二氢卟吩e6-C15单甲酯的合成工艺

doi: 10.3969/j.issn.1006-0111.2015.02.007

Optimization of synthesis of photosensitizer chlorin e6-C15 monomethyl ester by the orthogonal design

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正交设计优化光敏剂二氢卟吩e6-C15单甲酯的合成工艺

doi: 10.3969/j.issn.1006-0111.2015.02.007

1. 福建中医药大学药学院, 福建 福州 350108 2. 第二军医大学药学院, 上海 200433 3. 福建中医药大学药学院, 福建 福州 350108;第二军医大学药学院, 上海 200433

English Abstract

Optimization of synthesis of photosensitizer chlorin e6-C15 monomethyl ester by the orthogonal design

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正交设计优化光敏剂二氢卟吩e₆-C₁₅单甲酯的合成工艺

Optimization of synthesis of photosensitizer chlorin e₆-C₁₅ monomethyl ester by the orthogonal design

正交设计优化光敏剂二氢卟吩e₆-C₁₅单甲酯的合成工艺

1. 福建中医药大学药学院, 福建福州 350108

2. 第二军医大学药学院, 上海 200433

3. 福建中医药大学药学院, 福建福州 350108;第二军医大学药学院, 上海 200433

Optimization of synthesis of photosensitizer chlorin e₆-C₁₅ monomethyl ester by the orthogonal design