Design and synthesis of photosensitizer,13,15-cycloimides chlorin p6 / 药学实践杂志

ABSTRACT

Objective To design and prepare 13 ,15-cycloimides chlorin p6 (1) ,a class of chlorin related antitumor photo-sensitizers ,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 .