默克尔细胞癌（MCC）是一种罕见的侵袭性皮肤癌。从青霉属真菌中分离出两种新的异戊二烯化吲哚 2,5-二酮哌嗪生物碱：短短酰胺 E1 (1) 和 E2 (2)。两种化合物在低微摩尔范围内对选定的 MCC 细胞系（即 MCC13、MKL-1、UISO 和 WaGa）表现出中等的细胞毒活性。 1 和 2 的相对和绝对构型通过综合方法确定，包括 NOESY 光谱、DFT ECD 和 DP4 plus 计算以及 Marfey 反应。通过文献研究以及NMR和ECD数据的比较，对先前报道的三种天然类似物，诺托酰胺K和P以及asperversiamide L进行了结构修正。结构不稳定的1和2在中性水溶液条件下经历了稳定的相互转化。通过研究 2 在酸性甲醇溶液中的降解，鉴定出一种新的甲氧基化衍生物 (6) 和两种新的开环产物（7 和 8），其具有重排、伸长的 4-甲基戊-3-烯侧链。 HPLC 级甲醇的固有杂质（即甲醛）通过 aza-Cope 重排促进了 2 向 7 和 8 的轻松转化。

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 Penicillium fungus. 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 1 and 2 were 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 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.