Use of the chlorophyll derivative, purpurin-18, for syntheses of sensitizers for use in photodynamic therapy

Abstract

Reactions of purpurin-18 methyl ester 6 with various nucleophiles have been investigated as a means for synthesis of sensitizers for use in photodynamic therapy of tumours. Use of butylamine as the nucleophile resulted in ring-opening of the purpurin-18 anhydride ring to give a monoamide-γ-carboxylic acid 8, the purpurin-imide 11, and the di-amide-γ-carboxylic acid 12. When lysine or its esters were used as nucleophile, then lysylamide-γ-carboxylic acids 18, 20 and 23 were obtained, along with the purpurin lysyl-imides 21 and 22. Esterification and hydrolysis of the various carboxy functions were investigated as a means for obtaining stable water-soluble sensitizers. Similar reactions between ornithine and purpurin-18 methyl ester gave the corresponding ornithyl-chlorin-p₆ derivatives (e.g.31). The lysyl-chlorin-p₆18 was shown (in separate work) to be a highly effective tumour sensitizer.