Synthesis of antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A.
Antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A (1) have been synthesized starting from tribromoimidazole. A key step in the synthesis is the formation of the azepine ring via an intramolecular Buchwald coupling between a vinyl bromide and a N-methyl amide. This represents the first synthesis of a fully unsaturated imidazo[4,5,d]azepine. NMR data obtained for the synthetic ceratamine analogs has provided support for the structure assigned to the natural product.
Nodwell
Matt
M
Departments of Chemistry and Earth & Ocean Sciences, University of British Columbia, Vancouver, B.C., Canada.
Riffell
Jenna L
JL
Roberge
Michel
M
Andersen
Raymond J
RJ
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000737:chemistry*; D008938:Mitosis / Q000187:drug effects*; D015394:Molecular Structure; D011161:Porifera
D001381:Azepines; D007093:Imidazoles; C485389:ceratamine A