Benzoporphyrin derivatives: synthesis, structure and preliminary biological activity

Abstract

Starting from hematoporphyrin-IX dimethyl ester 1, a series of isomerically pure so-called benzoporphyrin derivatives (BPDs)20, 23–25, 27, 28, 31–33, 35–37, 39, 40, 42, 44 and 45 have been synthesized. The bis-porphyrins 46 and 47 with carbon–carbon linkages were also prepared by treating 3- and 8-(1-hydroxyethyl)benzoporphyrin derivatives 24 and 32 with triflic acid. In preliminary in vivo studies, the hexyl ether derivatives 27, 35, 40 and 45(as diastereoisomeric mixtures) appear to have better photosensitizing efficacy than the benzoporphyrin derivative monocarboxylic acid (BPD-MA; mixture of 21 and 22). Under similar doses and treatment conditions, other BPDs 23, 25, 26, 31, 33 and 34, along with bis-porphyrins 46 and 47 did not show any significant tumourcidal activity. The structures of the ring ‘A’ modified BPD isomers 20(cis) and 36(trans) were confirmed by single crystal X-ray studies.