Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6
-
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。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 λmax 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.
-
Key words:
- photodynamic therapy /
- photosensitizer /
- chlorine p6 /
- cycloimide /
- antitumor
-
[1] Agostinis P,Berg K,Cengel KA,et al. Photodynamic therapy of cancer:an update[J]. CA Cancer Clin,2011,61(4):250-281. [2] Abrahamse H,Hamblin MR. New photosensitizers for photodynamic therapy[J]. Biochem J,2016,473(4):347-364. [3] Dougherty TJ. An update on photodynamie therupy applications[J]. J Clin Laser Med Sur,2002,20(1):3-7. [4] Drogat N,Gady C,Granet R,et al. Design and synthesis of water-soluble polyaminated chlorins and bacteriochlorins with nearinfrared absorption[J]. Dyes Pigments,2013,98:609-614. [5] Oliveira KT,Momo PB,Assis FF,et al. Chlorins:natural sources,synthetic developments and main applications[J]. Curr Org Synth,2014,11(1):42-58. [6] Meng Z,Yu B,Han G,et al. Chlorin p6-based water-soluble amino acid derivatives as potent photosensitizers for photodynamic therapy[J]. J Med Chem,2016,59:4999-5010. [7] 沈卫镝,姚建忠,方勇,等. 叶绿素a降解产物紫红素-18的光动力效应[J]. 中国医药工业杂志,2001,32(5):217-219. [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):403-406. [9] 王进军,韩光范,邬旭然,等. 叶绿素-a及其衍生物的Qy轴向氧化反应和E-环重排反应[J]. 有机化学,2005,25(1):101-108. -
![WeChat](/fileYXSJZZ/journal/article/yxsjzz/2017/1/PIC/wechat_cn_20170107.jpg)
计量
- 文章访问数: 3684
- HTML全文浏览量: 429
- PDF下载量: 623
- 被引次数: 0