Biarylic biscarbazole alkaloids: occurrence, stereochemistry, synthesis, and bioactivity.
The structurally and pharmacologically intriguing but stereochemically initially disregarded small class of biarylic biscarbazole alkaloids is presented, starting with an introduction of the different structural patterns found in nature. For the construction of the biaryl bond, mainly biomimetic oxidative coupling reactions were used, as shown for the natural products bismurrayaquinone-A, bis-2-hydroxy-3-methylcarbazole, clausenamine-A, and murrastifoline-F. For most of these compounds, a resolution of the respective atropo-enantiomers succeeded either directly, by high-performance liquid chromatography by HPLC on a chiral phase, or via atropo-diastereomers, after derivatization with a chiral auxiliary. The absolute configurations of the pure enantiomers were assigned by comparison of experimental (CD) spectra with those quantum chemi-cally calculated, or, for atropo-diastereomeric derivatives, by means of ROESY investigations and X-ray crystallography. Ullmann-type coupling conditions were also found to be feasible for the construction of the 2,2'-biscarbazole core, necessitating a completely regioselective 2-bromination protocol. The first atroposelective synthesis of such a basic target structure was achieved by application of the "lactone methodology," giving rise to an atropisomeric ratio of 85 : 15. Some of the biscarbazole alkaloids and their derivatives were found to have interesting bioactivities, and for the first time, the natural atropo-enantiomeric ratio in the plants was determined for one of these compounds, murrastifoline-F.
Tasler
Stefan
S
Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Bringmann
Gerhard
G
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007202:Indicators and Reagents; D007783:Lactones / Q000737:chemistry; D008968:Molecular Conformation; D010946:Plants, Medicinal / Q000737:chemistry
D000470:Alkaloids; D007202:Indicators and Reagents; D007783:Lactones