| Autor: |
Khong, Quan T., Smith, Emily A., Wendt, Karen L., Dalilian, Masoumeh, Goncharova, Ekaterina I., Brownell, Isaac, Cichewicz, Robert H., Henrich, Curtis J., Beutler, John A., O’Keefe, Barry R., Du, Lin |
| Zdroj: |
Journal of Natural Products; July 2024, Vol. 87 Issue: 7 p1826-1837, 12p |
| Abstrakt: |
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicilliumfungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1and 2were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey’s reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1and 2underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2to 7and 8was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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