二氢卟吩p6-13,15-环酰亚胺类光敏剂的设计合成

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

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(1 H 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。

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 chlorophyll a ,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 1 H 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.