Alkyl ether analogs of chlorophyll-a derivatives .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 chiorophyll-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 12-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 chlorin e(6) 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 pyropheophorbide-a methyl ester and chlorin e(6) trimethyl ester have long wavelength absorption at 660 nm (epsilon 45000 to 50000), Reduction of the carbonyl group in the pyropheophorbide-a to methylene (ring E) resulted in a blue shift to 648 nm (epsilon 38 000).