二氢卟吩p6-13,15-环酰亚胺类光敏剂的设计合成

刘明辉; 刘俊宏; 韩贵焱; 张星杰; 盛春泉; 姚建忠

doi:10.3969/j.issn.1006-0111.2017.01.007

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二氢卟吩p6-13,15-环酰亚胺类光敏剂的设计合成

刘明辉, 刘俊宏, 韩贵焱, 张星杰, 盛春泉, 姚建忠

文章导航 > 药学实践与服务 > 2017 > 35(1): 26-30,35

刘明辉, 刘俊宏, 韩贵焱, 张星杰, 盛春泉, 姚建忠. 二氢卟吩p6-13,15-环酰亚胺类光敏剂的设计合成[J]. 药学实践与服务, 2017, 35(1): 26-30,35. doi: 10.3969/j.issn.1006-0111.2017.01.007

引用本文:

LIU Minghui, LIU Junhong, HAN Guiyan, ZHANG Xingjie, SHENG Chunquan, YAO Jianzhong. Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(1): 26-30,35. doi: 10.3969/j.issn.1006-0111.2017.01.007

Citation:

LIU Minghui, LIU Junhong, HAN Guiyan, ZHANG Xingjie, SHENG Chunquan, YAO Jianzhong. Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(1): 26-30,35. doi: 10.3969/j.issn.1006-0111.2017.01.007

二氢卟吩p6-13,15-环酰亚胺类光敏剂的设计合成

doi: 10.3969/j.issn.1006-0111.2017.01.007

1.
福建中医药大学药学院, 福建福州 350122
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 350122;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（11431920400、11431920401）

Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6

1.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
2.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China
3.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

摘要: 目的设计合成比紫红素-18（ 2 ）化学性质更稳定的二氢卟吩p6-13，15-环酰亚胺类光敏剂（ 1 ）。方法以蚕沙叶绿素a粗提物（糊状叶绿素）酸水解产物脱镁叶绿酸a（ 3 ）的五元β-酮基羧酸酯环经碱性条件下空气氧化降解制得的紫红素-18（ 2 ）为原料，用各种胺包括羧基保护的氨基酸与其酸酐环发生缩合反应制得目标化合物。结果以32.6%~65.2%的收率成功合成了目标化合物 1a ~ 1j ，其结构经电喷雾质谱（ESI-MS）、氢谱（¹H NMR）、紫外谱（UV）和元素分析确证。结论紫红素-18（ 2 ）和胺反应可以制得目标化合物 1 。该合成路线具有原料廉价易得、反应条件温和、操作简便等优点。
- 光动力治疗 /
- 光敏剂 /
- 二氢卟吩p6 /
- 环酰亚胺 /
- 抗肿瘤
Abstract: Objective To design and prepare 13,15-cycloimides chlorin p6 ( 1 ),a class of chlorin related antitumor photosensitizers,which contain a more stable six-membered cyclic imide comparing to the exocyclic anhydride ring of purpurin-18 ( 2 ). Compounds ( 1 ) exhibit strong absorption at long wavelengths near λ_max 700 nm to take full advantage of greater tissue penetration. Methods Pheophorbide a ( 3 ) was obtained by acid hydrolysis of chlorophylla,which was from crude chlorophyll extracts of Chinese traditional herb named Silkworm excrement. Purpurin-18 ( 2 ) was prepared by air oxidation and alkali open loop simultaneously on five-membered beta-keto carboxylic ester ring of pheophorbide a ( 3 ). Finally,the target compounds 1a ~ 1j were synthesized via condensation of its anhydride ring with various amines including carboxyl-protected amino acids. Results Target compounds 1a ~ 1j were successfully synthesized in yields ranged from 32.6% to 65.2%. Their structures were confirmed by elemental analysis,ESI-MS and ¹H NMR spectra. Conclusion Treatment of purpurin-18 ( 2 ) with amines can produce target compounds 1a ~ 1j . The starting raw material was inexpensive and readily available. The reaction conditions were mild and workup was convinient.
- photodynamic therapy /
- photosensitizer /
- chlorine p6 /
- cycloimide /
- antitumor

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二氢卟吩p6-13,15-环酰亚胺类光敏剂的设计合成

doi: 10.3969/j.issn.1006-0111.2017.01.007

1. 福建中医药大学药学院, 福建福州 350122

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 350122;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（11431920400、11431920401）

收稿日期: 2016-11-16
修回日期: 2016-12-12

关键词:

光敏剂 /

摘要: 目的设计合成比紫红素-18（ 2 ）化学性质更稳定的二氢卟吩p6-13，15-环酰亚胺类光敏剂（ 1 ）。方法以蚕沙叶绿素a粗提物（糊状叶绿素）酸水解产物脱镁叶绿酸a（ 3 ）的五元β-酮基羧酸酯环经碱性条件下空气氧化降解制得的紫红素-18（ 2 ）为原料，用各种胺包括羧基保护的氨基酸与其酸酐环发生缩合反应制得目标化合物。结果以32.6%~65.2%的收率成功合成了目标化合物 1a ~ 1j ，其结构经电喷雾质谱（ESI-MS）、氢谱（¹H NMR）、紫外谱（UV）和元素分析确证。结论紫红素-18（ 2 ）和胺反应可以制得目标化合物 1 。该合成路线具有原料廉价易得、反应条件温和、操作简便等优点。

English Abstract

Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

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

3. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2016-11-16
Rev Recd Date: 2016-12-12

Keywords:

Abstract: Objective To design and prepare 13,15-cycloimides chlorin p6 ( 1 ),a class of chlorin related antitumor photosensitizers,which contain a more stable six-membered cyclic imide comparing to the exocyclic anhydride ring of purpurin-18 ( 2 ). Compounds ( 1 ) exhibit strong absorption at long wavelengths near λ_max 700 nm to take full advantage of greater tissue penetration. Methods Pheophorbide a ( 3 ) was obtained by acid hydrolysis of chlorophylla,which was from crude chlorophyll extracts of Chinese traditional herb named Silkworm excrement. Purpurin-18 ( 2 ) was prepared by air oxidation and alkali open loop simultaneously on five-membered beta-keto carboxylic ester ring of pheophorbide a ( 3 ). Finally,the target compounds 1a ~ 1j were synthesized via condensation of its anhydride ring with various amines including carboxyl-protected amino acids. Results Target compounds 1a ~ 1j were successfully synthesized in yields ranged from 32.6% to 65.2%. Their structures were confirmed by elemental analysis,ESI-MS and ¹H NMR spectra. Conclusion Treatment of purpurin-18 ( 2 ) with amines can produce target compounds 1a ~ 1j . The starting raw material was inexpensive and readily available. The reaction conditions were mild and workup was convinient.