Biarylic Biscarbazole Alkaloids: Occurrence, Stereochemistry, Synthesis, and Bioactivity

Abstract

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.

Efficient and Simple Synthesis of 6-Aryl-1,4-dimethyl-9H-carbazoles

“…This methodology allows us to prepare new derivatives with potent interest in cancerology, especially biscarbazoles similar to Clausenamine A (Figure 2) [16,17,18,19]. …”

Synthesis of carbazoloquinone natural products ‘on-water’

“…15,16 The isolation of murrayaquinone B (11) represented the first report of a naturally occurring carbazoloquinone. 20,21 As yet, there are no reports detailing total syntheses of the remaining murrayaquinones C-E (12)(13)(14) or pyrayaquinone C (27). Moody and co-worker developed a one-pot Claisen rearrangement -Hemetsberger indole synthesis en route to the natural product.…”

“…Pyrayaquinones C (27) and B (28) (Scheme 10) were isolated from the same natural source as the murrayaquinones and feature a related architecture in which the geranyl and prenyl units have cyclised to give the 6-membered rings. 22,23 Ramesh and Kapil reported a synthesis of pyrayaquinone B (28) that features a DDQ oxidation, 11 while Furukawa and co-workers utilised a palladium-mediated oxidative coupling to access compound 28.…”

Naturstoffhybride als neue Leitstrukturen bei der Wirkstoffsuche

“…[2] Sie spielen eine wichtige Rolle als hochwirksame Insektizide (z. B. Pyrethrin (9) und Spinosyn A (10 a) und D (10 b)) oder Fungizide (z. B. Analoga von Strobilurin A (11)).…”

“…Hiervon sind lediglich 14 Verbindungen bekannt, die alle aus Pflanzen der zwei Rutaceae-Gattungen, Clausena und Murraya S., isoliert wurden. [9] Das charakteristische Strukturmerkmal dieser Alkaloide ist ebenfalls eine stereogene Achse. In diesen Pflanzen werden auch über eine C-N-Bindung verknüpfte Dimere wie 21 gefunden.…”