Di-Isatropolone C, a Spontaneous Isatropolone C Dimer Derivative with Autophagy Activity

Author:

Fu Jie1,Liu Xiaoyan1,Zhang Miaoqing1,Liu Jiachang1,Li Shufen1,Jiang Bingya1,Wu Linzhuan1

Affiliation:

1. CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Abstract

Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability. The plausible molecular mechanism for di-isatropolone C formation is proposed, in which complex dehydrogenative C-C bond coupling may have happened to connect the two isatropolone C monomers. Like isatropolone C, di-isatropolone C shows the biological activity of inducing autophagy in HepG2 cells.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

The National Microbial Resource Center

Publisher

MDPI AG

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