Uncovering the structure of human red hair pheomelanin: benzothiazolylthiazinodihydroisoquinolines as key building blocks

J Nat Prod. 2011 Apr 25;74(4):675-82. doi: 10.1021/np100740n. Epub 2011 Feb 22.

Abstract

Biomimetic oxidation of the pheomelanin precursor 5-S-cysteinyldopa in the presence of Zn(2+) ions led to the isolation of two isomeric products, one of which could be identified as the benzothiazolylthiazinodihydroisoquinoline 5, while the other proved too unstable for a complete characterization. Both these products were converted into more stable oxidized forms, which after ethylchloroformate derivatization were characterized as the ethyl ester/ethoxycarbonyl isoquinolines 8 and 9. Compound 5 exhibited absorption characteristics similar to those of red hair pheomelanin, including a main band around 400 nm in acids. Similarly to red hair pheomelanin and synthetic pigments, 5 afforded on chemical degradation a thiazolylpyridinecarboxylic acid fragment. Model chemical studies allowed the proposal of a formation mechanism for the benzothiazole and dihydroisoquinoline systems in compound 5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzothiazoles / chemistry
  • Benzothiazoles / metabolism*
  • Cysteinyldopa / biosynthesis*
  • Cysteinyldopa / chemistry
  • Hair / chemistry
  • Hair / metabolism
  • Hair Color / physiology*
  • Humans
  • Isoquinolines / chemistry
  • Isoquinolines / metabolism*
  • Melanins / biosynthesis*
  • Melanins / chemistry*
  • Melanins / physiology
  • Models, Chemical*
  • Molecular Structure
  • Oxidation-Reduction
  • Pigments, Biological / biosynthesis*
  • Pigments, Biological / chemistry
  • Stereoisomerism
  • Zinc / chemistry

Substances

  • Benzothiazoles
  • G 1617
  • Isoquinolines
  • Melanins
  • Pigments, Biological
  • pheomelanin
  • Cysteinyldopa
  • benzothiazole
  • Zinc