部分
化学
内酰胺
立体化学
二聚体
圆二色性
酶
单体
生物化学
有机化学
聚合物
作者
Jimei Liu,Zhenfei Wang,Jun Wu,Yaotian Han,Fei Ye,Tiantai Zhang,Haibo Yu,Zheng-Shun Wen,Jungui Dai
标识
DOI:10.1016/j.cclet.2023.108363
摘要
Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity, exhibiting a wide of biological properties, especially for the lactam derivatives consisting a γ-lactam moiety and N-linked side chains. These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways. Stachbotrydial (2) with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines. In the present work, an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono- and diamines in the fungus Stachybotrys chartarum cultures. In total, 24 phenylspirodrimane lactams (1, 3–25) including 18 new compounds were synthesized. Among them, stachybocin A (1), a bioactive phenylspirodrimane lactam dimer, was produced with the yield of 18.7 mg/g of cell dry weight. The structures of these compounds were elucidated by extensive spectroscopic data, single-crystal X-ray diffraction (Cu Kα), and calculated electronic circular dichroism (ECD) analyses. Bioassay revealed that compounds 1, 17, and 24 displayed significant inhibitory effect on the inactivated state of hNaV 1.2 channels with IC50 values of 0.22, 2.08, and 0.53 μmol/L, respectively. In addition, 1 showed potent protein tyrosine phosphatase 1B (PTP1B) inhibitory, N-methyl-D-aspartate (NMDA) receptor antagonistic, and anti-inflammatory activities.
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