| Summary: | Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (<b>15</b>) 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<sub>6</sub> aspartic acid conjugate as (<b>13</b>), NMR and other synthetic procedures described herein arrived at the correct structure (<b>15</b>), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e<sub>6</sub> chemistry (including the intramolecular formation of an anhydride (<b>24</b>)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 13<sup>1</sup> (formic), 15<sup>2</sup> (acetic), and 17<sup>3</sup> (propionic) of chlorin e<sub>6</sub> (<b>14</b>). Cellular investigations of several amino acid conjugates of chlorin-e<sub>6</sub> revealed that the 13<sup>1</sup>-aspartylchlorin-e<sub>6</sub> derivative is more phototoxic than its 15<sup>2</sup>- and 17<sup>3</sup>-regioisomers, in part due to its nearly linear molecular conformation.
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