Alkyl ether analogs of chlorophyll-a derivatives: Part 1. Synthesis, photophysical properties and photodynamic efficacy
The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-a analogs are described. For short-chain carbon ethers (1-7 carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n- hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1- bromoethyl)-2-devinylpyropheophorbide-a with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-a analogs were found to be more active than related chlorine, derivatives, in which the isocyclic ring (ring 'E') was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-a analogs. The photosensitizers prepared from pyropheophorhide-a methyl ester and chlorine6 trimethyl ester have lung wavelength absorption at 660 nm (ε 45000 to 50000). Reduction of the carbonyl group in the pyrophenphorbide-a to methylene (ring E) resulted in a blue shift to 648 nm (ε 38000).
Publication Source (Journal or Book title)
Photochemistry and Photobiology
Pandey, R., Sumlin, A., Constantine, S., Aoudia, M., Potter, W., Bellnier, D., Henderson, B., Rodgers, M., Smith, K., & Dougherty, T. (1996). Alkyl ether analogs of chlorophyll-a derivatives: Part 1. Synthesis, photophysical properties and photodynamic efficacy. Photochemistry and Photobiology, 64 (1), 194-204. https://doi.org/10.1111/j.1751-1097.1996.tb02442.x