Chlorophyll-a derivatives in photodynamic therapy: effect of position of heptyl ether side-chains on in vivo photosensitizing activity

Syntheses and comparative in vivo photosensitizing efficacy of a series of chlorophyll-a derivatives with (1-heptyloxyethyl) substituents at various positions are discussed. Compared with Photofrin®, the n-heptyl ether analogues showed better in vivo sensitizing activity (DBA/2 mice transplanted with SMT/F tumors) as well as reduced skin phototoxicity. The Vilsmeier formylation of copper(II) methyl mesopyropheophorbide-a 11 did not produce the expected meso-formyl derivative 12, but instead gave the α,β-unsaturated chloroformyl analogue 13 as the major product.