Design and Synthesis of Novel Phenothiazinium Photosensitiser Derivatives

Abstract

Abstract A high‐yielding approach towards N ‐(2‐aminoethyl)‐Azure B has been established and extended towards the preparation of a functionalized peptide‐dye synthetic precursor; Boc‐protected 3‐(alkylamino)phenothiazin‐5‐ium TFA. This has been utilized in a series of reactions with various amines towards nine novel 3,7‐disubstituted phenothiazin‐5‐ium derivatives. Cleavage of the Boc group in the 3,7‐disubstituted salts allowed a further seven novel dyes to be prepared and these have been utilized in a practical methodology designed for the synthesis of 13 novel phenothiazine‐peptide conjugates. These peptide‐photosensitizer vectors consist of a covalent attachment of a tethered dye to various protected amino acid moieties including the cell‐penetrating peptide (CPP) octa‐arginine and exhibit intense absorption maxima in the 623–650 nm regions of the visible spectrum. The main goal of the studies is the design of cell‐compatible photosensitisers that may be employed in photodynamic therapy.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)