Red Hair 1,4-Benzothiazines: from Human Pigmentation to Functional Dyes

The 2H-1,4-benzothiazines represent a unique group of naturally occurring heterocyclic compounds, which derive biogenetically from tyrosine and cysteine via a mutation-induced deviation of the melanin pathway to provide the core structure of the red human hair pigments pheomelanins. Since the elucidation of the biosynthetic pathway of pheomelanins in the 1960s, 1,4-benzothiazines and red hair pigments have been the focus of interest due to their compelling biomedical significance in relation to the high susceptibility of red heads to skin cancer and melanoma.[1] Model studies have gradually shed light on a number of remarkable physical and chemical properties of benzothiazine-based systems, e.g. the robust bibenzothiazine visible chromophore; the photosensitizing action of central relevance to the proness of red haired subjects to actinic damage, the remarkable chemical, paramagnetic and redox cycling properties of benzothiazine-based polymers (synthetic pheomelanins); and the wide diversity of molecular scaffolds that may originate from biomimetic or synthetic manipulations of the benzothiazine systems, through metal ion-dependent control on decarboxylation pathways or unusually facile ring-contraction processes. [2] Recently, the formation and stereochemistry of the 2,2’bi(2H-1,4-benzothiazine) system, the photoactive motif of pheomelanins, was examined by a combined experimental and computational approach, and its potential as a unique photochromic and acidi chromic four state system was evaluated e.g. for application in reversible writing processes. [3a] Similarly the green blue 2,2’-bi(2H-1,4-benzothiazine) generated by dehydrogenative coupling of the 3-phenyl-1,4-benzothiazine proved of potential practical interest for colorimetric peroxide and redox biometal detection. [3b] These and other results will be presented with the aim of highlighting the chemistry of red hair benzothiazines as a novel source of inspiration in the quest for innovative scaffolds and Nature-mimicking functional systems.