College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian 116044, China.
Pharmaceutical Research Center, Second Affiliated Hospital, Dalian Medical University, Dalian 116027, China.
Org Biomol Chem. 2022 Mar 23;20(12):2508-2517. doi: 10.1039/d2ob00053a.
Biseuphoids A (1) and B (2), two unprecedented -abietane-type diterpenoid dimers linked by monomeric blocks through C-17-C-12' and C-17-C-11', respectively, were isolated from , along with their biogenesis related diterpenoid monomers, 17-hydroxyjolkinolide B (3), caudicifolin (4), and fischeriabietane C (5). Their structures were elucidated by extensive spectroscopy assisted by quantum chemical NMR and ECD calculations. The unusual dimeric skeletons are possibly derived from the adduct of diterpenoid monomers through Michael-like reactions. The novel dimers 1 and 2 exhibited inhibitory activities on soluble epoxide hydrolase (sEH) with IC values of 8.17 and 5.61 μM, respectively. Molecular dynamics studies illustrated that both 1 and 2 can occupy the catalytic pocket of sEH by forming stable hydrogen bonds with the key amino acid residues including Gln384, Asn378, Pro361, Ala365, Asn366, and Asn472.
双贝壳烯 A（1）和 B（2）是两种前所未有的 -abietane 型二萜二聚体，分别通过单体块通过 C-17-C-12'和 C-17-C-11'连接，与它们的生物发生相关的二萜单体 17-羟基乔卡林内酯 B（3）、根皮苷（4）和 Fischeriabietane C（5）一起从 中分离出来。通过量子化学 NMR 和 ECD 计算辅助的广泛光谱学阐明了它们的结构。不寻常的二聚体骨架可能是通过二萜单体的加成反应通过迈克尔型反应衍生而来的。新型二聚体 1 和 2 对可溶性环氧化物水解酶 (sEH) 表现出抑制活性，IC 值分别为 8.17 和 5.61 μM。分子动力学研究表明，1 和 2 都可以通过与包括 Gln384、Asn378、Pro361、Ala365、Asn366 和 Asn472 在内的关键氨基酸残基形成稳定的氢键，占据 sEH 的催化口袋。
