Biomimetic total synthesis and antimicrobial evaluation of anachelin H.
The first biomimetic total synthesis of the iron chelator anachelin H isolated from the cyanobacterium Anabaena cylindrica is reported. A first generation approach delivered one enantiomeric series of the polyketide fragment. Comparison of the 1H NMR data suggested the relative configuration of this anachelin fragment. The relative and absolute configuration of anachelin H was then established by total synthesis. A second generation approach involved the enzymatic conversion of N,N-dimethyltyramine to the anachelin chromophore. It was demonstrated that the enzyme tyrosinase is activated by the product during this reaction, the anachelin chromophore can serve as a tyrosinase activator. Anachelin H was evaluated against a panel of eleven bacterial and fungal pathogens, and moderate antibiotic activity (32 microg/mL) against Moraxella catarrhalis was found.
Gademann
Karl
K
Chemical Synthesis Laboratory, Swiss Federal Institute of Technology (EPFL), SB-ISIC-LSYNC, CH-1015 Lausanne, Switzerland. karl.gademann@epfl.ch
Bethuel
Yann
Y
Locher
Hans H
HH
Hubschwerlen
Christian
C
D046868:Anabaena cylindrica / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D032701:Biomimetics; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D001936:Moraxella catarrhalis / Q000187:drug effects*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011806:Quinolinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009842:Oligopeptides; D011806:Quinolinium Compounds; C525348:anachelin H