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UBC Theses and Dissertations

Chlorin-like photosensitizers for photodynamic therapy Liu, Xin

Abstract

The goal of the project was to generate new photosensitizers for use in photodynamic therapy (PDT) by modifying the amphiphilicity of the tetrapyrrolic macrocycles. This aim was achieved by developing the chemistry of the conjugated vinyl group on tetrapyrrolic macrocycles. In the first part, the non-diastereomeric primary ether derivatives of pyropheophorbide a, 60, and ether derivatives of ring B-BPD-1,3-diene dimethyl ester, 62, were synthesized successfully. New synthetic methods for the intermediates and target compounds were developed and proven to be effective, convenient and safe. Preliminary PDT cytotoxicity assays showed that some of the primary ether derivatives exhibited promising PDT efficacy. Secondly, cross-metathesis (CM) was applied successfully to vinylchlorin and vinylporphyrin substrates by employing the imidazolylidene ruthenium benzylidene catalyst 96. The optimized reaction conditions and the reactivity of different substrates towards CM were investigated. A variety of chlorins and porphyrins with the substituted-vinyl groups, such as 105, 113, 123, 124, 135 and 125, were synthesized via cross-metathesis in good yields with excellent E-stereoselectivity. This method has proven to be a generalizable strategy for modifying the amphiphilicity of tetrapyrrolic macrocycles starting with the conjugated vinyl group. [Please refer to dissertation for diagrams.]

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