Asperosin A, a [4 + 2] Diels–Alder cycloaddition polyketide dimer from Aspergillus rugulosa with immunosuppressive activity

Yuben Qiao; Xiaosheng Tan; Qianqian Xu; Zijun Zhang; Qiaoxin Xu; Li Tao; Junjun Liu; Hucheng Zhu; Chunmei Chen; Ying Ye; Yuanyuan Lu; Gang Chen; Changxing Qi; Yonghui Zhang

doi:10.1039/D1QO01767E

Asperosin A, a [4 + 2] Diels–Alder cycloaddition polyketide dimer from Aspergillus rugulosa with immunosuppressive activity†

Yuben Qiao,

‡^a Xiaosheng Tan,‡^b Qianqian Xu,‡^a Zijun Zhang,^a Qiaoxin Xu,^a Li Tao,^c Junjun Liu,

^a Hucheng Zhu,^a Chunmei Chen,^a Ying Ye,^a Yuanyuan Lu,^d Gang Chen,*^b Changxing Qi*^a and Yonghui Zhang

*^a

Author affiliations

* Corresponding authors

^a Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China
E-mail: zhangyh@mails.tjmu.edu.cn, qichangxing@hust.edu.cn

^b Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China
E-mail: gchen@tjh.tjmu.edu.cn

^c Ezhou Central Hospital, Ezhou 436000, People's Republic of China

^d Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, People's Republic of China

Abstract

A novel homologous polyketide dimer, asperosin A (1), constructed with a unique hetero-bicycle 6/5 ring system featuring four continuous quaternary carbons, was isolated from a solid culture of the fungus Aspergillus rugulosa. The structure of 1 was elucidated by extensive 400 MHz and 600 MHz nuclear magnetic resonance (NMR) spectroscopy analysis, electronic circular dichroism (ECD) calculations, DP4⁺ probability analysis, and a detailed discussion of its biosynthetic origin. Biogenetically, compound 1 was constructed from two identical original polyketides via the intermolecular [4 + 2] Diels–Alder cycloaddition reaction. It is notable that compound 1 displayed remarkable immunosuppressive activity in murine splenocytes and human T cells stimulated by anti-CD3/anti-CD28 monoclonal antibodies.

Organic Chemistry Frontiers

Asperosin A, a [4 + 2] Diels–Alder cycloaddition polyketide dimer from Aspergillus rugulosa with immunosuppressive activity†

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Asperosin A, a [4 + 2] Diels–Alder cycloaddition polyketide dimer from Aspergillus rugulosa with immunosuppressive activity

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