A New Insight in the Biosynthesis of Pheomelanins: Characterization of a Labile 1,4-Benzothiazine Intermediate.
It has long been known that pheomelanins, the distinctive pigments of red hair and celtic skin, arise by the oxidative cyclization of cysteinyldopas, mainly the 5-S-isomer 1, via 1,4-benzothiazines. However, the nature and reactivity of these intermediates have remained poorly defined. In an reexamination of the oxidation of 1, in aqueous buffers at physiological pHs, a hitherto unknown labile intermediate was identified and formulated as the 3-hydroxy-3,4-dihydro-1,4-benzothiazine 5 based on direct NMR analysis of the reaction mixture and conversion to the stable benzothiazines 3 and 4 under different conditions. Structure 5 was further supported by oxidation of the model compound 6 leading to the analogous more stable 2,2-dimethyldihydro-1,4-benzothiazine 9.
Napolitano
Alessandra
A
Department of Organic and Biological Chemistry, University of Naples "Federico II", Via Mezzocannone 16, I-80134 Naples, Italy.
Memoli
Sofia
S
Prota
Giuseppe
G