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在 NAD(+)依赖的组蛋白去乙酰化酶抑制剂存在下培养的毛壳菌产生的新型 C13-聚酮化合物的结构多样性。

Structural diversity of new C13-polyketides produced by Chaetomium mollipilium cultivated in the presence of a NAD(+)-dependent histone deacetylase inhibitor.

机构信息

Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan.

出版信息

Org Lett. 2012 Nov 2;14(21):5456-9. doi: 10.1021/ol302539s. Epub 2012 Oct 19.

Abstract

Cultivation of Chaetomium mollipilium with nicotinamide, a NAD(+)-dependent HDAC inhibitor, stimulated its secondary metabolism, leading to the isolation of structurally diverse new C(13)-polyketides, mollipilin A-E (1-5) as well as two known compounds (6 and 7). Spectroscopic methods, X-ray single crystal diffraction analysis, and VCD elucidated the absolute configurations of structures 1-6, and plausible biosynthetic pathways for 1-7 were proposed based on structural relationships. Mollipilins A (1) and B (2) exhibited moderate growth inhibitory effects on HCT-116 cells.

摘要

用烟酰胺(一种 NAD(+) 依赖性 HDAC 抑制剂)培养卷枝毛壳菌,可刺激其次级代谢,从而分离出结构多样的新型 C(13)-聚酮化合物,包括 mollipilin A-E(1-5)以及两种已知化合物(6 和 7)。通过光谱方法、X 射线单晶衍射分析和 VCD 确定了 1-6 的绝对构型,并根据结构关系提出了 1-7 的可能生物合成途径。Mollipilins A(1)和 B(2)对 HCT-116 细胞表现出中等的生长抑制作用。

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