Amino Acid Derivatives of Chlorin-e 6 -A Review.

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 ( 15 ) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e 6 aspartic acid conjugate as ( 13 ), NMR and other synthetic procedures described herein arrived at the correct structure ( 15 ), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e 6 chemistry (including the intramolecular formation of an anhydride ( 24 )) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 13 1 (formic), 15 2 (acetic), and 17 3 (propionic) of chlorin e 6 ( 14 ). Cellular investigations of several amino acid conjugates of chlorin-e 6 revealed that the 13 1 -aspartylchlorin-e 6 derivative is more phototoxic than its 15 2 - and 17 3 -regioisomers, in part due to its nearly linear molecular conformation.