Notoamides A–D: Prenylated Indole Alkaloids Isolated from a Marine‐Derived Fungus, Aspergillus sp.

Abstract

Aus dem Meer: Die Strukturen und Konfigurationen von vier neuen Indolalkaloiden aus dem aus Muscheln stammenden Pilz Aspergillus sp., den Notoamiden A–D, wurden bestimmt. Die Notoamide A–C sind moderat zytotoxisch gegen Krebszelllinien. Die Beziehung zwischen ihnen und anderen Metaboliten spricht dafür, dass der Pilz einen vielseitigen Biosyntheseweg nutzt.

Isolation, Structure Elucidation, and Biomimetic Total Synthesis of Versicolamide B, and the Isolation of Antipodal (−)‐Stephacidin A and (+)‐Notoamide B from Aspergillus versicolor NRRL 35600

“…described by Tsukamoto and co-workers. [5] The occurrence of (À)-stephacidin A and its presumed oxidation metabolite (+)-notoamide B in the same stereochemical series, but distinct from that reported from these other Aspergillus isolates, is striking. If the proposed biogenesis based on IMDA construction is correct, this would mandate that each fungal species evolved a means by which to select for the production of one enantiomeric cycloadduct (that is, (+)-or (À)-stephacidin A).…”

“…[1a, 4] The synthesized compounds include brevianamide B (10), stephacidin A (3), marcfortine C, and the recently discovered fungal metabolite notoamide B (6; Scheme 1). [4,5] We demonstrate herein that this general strategy was easily amendable to the total synthesis of versicolamide B and provided unambiguous structural and relative stereochemical corroboration for this stereochemically unique natural product.…”

“…Five "known" compounds (sterigmatocystin, brevianamide F, stephacidin A, norgeamide D, and notoamide B) were obtained from this extract. The structures of four of the known compounds were confirmed by comparison of their NMR and MS data with literature values, [7] while the structure of notoamide B was independently assigned because the report describing this metabolite [5] had not yet appeared in the literature. Sterigmatocystin was a major component, and appeared to be responsible for most of the anti-insectan activity of the crude extract.…”

“…These data, along with the CD spectra, rigorously support the surprising fact that Aspergillus versicolor NRRL 35600 produces the opposite enantiomers of stephacidin A and notoamide B to those obtained from the related fungi Aspergillus ochraceus WC76466 and from the marine-derived Aspergillus sp., which were studied by Tsukamoto and co-workers. [5] The structure and relative configuration of versicolamide B were corroborated through a biomimetic, racemic total synthesis. Our synthesis of 8 commenced with a Mitsonobutype elimination (PBu 3 , DEAD) of the recently prepared alcohol 11 [4] to afford an intermediate enamide, which was then treated with Me 3 OBF 4 and Cs 2 CO 3 to cleanly provide the desired lactim ether 12 in good yield (Scheme 3).…”

“…[5] We have further determined that the (À)-stephacidin A sample collected from A. versicolor is optically pure by HPLC on a chiral stationary phase (see the Supporting Information). These data, along with the CD spectra, rigorously support the surprising fact that Aspergillus versicolor NRRL 35600 produces the opposite enantiomers of stephacidin A and notoamide B to those obtained from the related fungi Aspergillus ochraceus WC76466 and from the marine-derived Aspergillus sp., which were studied by Tsukamoto and co-workers.…”