Résumé

The cyanobacterial metabolite anachelin, postulated to serve as a biological ligand to Fe (siderophore), is composed of a fascinating blend of polyketide, peptide, and alkaloid building blocks. In particular, the latter consists of a N,N-dimethyltetrahydroquinolinium fragment, of which the biosynthesis is unknown. To investigate the role of this permanently positive charged fragment, a synthesis of both the anachelin chromophore and its bis-nor derivative lacking the N,N-di-Me groups was developed starting from suitably protected nitro-DOPA in six and five steps, resp., and in 50-64% overall yield. Both compounds were then compared for their chemical behavior toward oxidation. It was found that the bis-nor-anachelin chromophore is readily oxidized in solution in the presence of air, with a clear dependence of the rate of oxidation on the pH value. In addition, we could demonstrate that the enzyme tyrosinase, postulated to serve as key catechol oxidase in the biosynthesis of anachelin, also oxidized the bis-nor-hydroquinonamine deriv. Last, Fe(III) was shown to be an effective oxidant for the bis-nor-anachelin chromophore, resulting in all cases in the corresponding aminoquinone. In stark contrast, the anachelin chromophore resisted oxidation under various conditions surveyed (i.e., mediated by air, by tyrosinase, and by Fe(III)). In particular, Fe(III) was readily complexed by the anachelin chromophore, and the resulting complexes were characterized. In conclusion, these experiments demonstrate that the bis-nor-anachelin chromophore is unlikely to serve as cyanobacterial ligand, due to its instability toward oxidation. Moreover, the permanent quaternary ammonium group in anachelin renders the alkaloid chromophore much more stable against oxidation and thus results in its use as ligand for Fe (III).

Détails