Beshanzoides A-D, unprecedented cycloheptanone-containing polyketides from Penicillium commune P-4-1, an endophytic fungus of the endangered conifer Abies beshanzuensis

Hao-Wei Chen; Chun-Xiao Jiang; Jiyang Li; Na Li; Yi Zang; Xi-Ying Wu; Wen-Xue Chen; Juan Xiong; Jia Li; Jin-Feng Hu

doi:10.1039/d1ra08377e

Beshanzoides A-D, unprecedented cycloheptanone-containing polyketides from Penicillium commune P-4-1, an endophytic fungus of the endangered conifer Abies beshanzuensis

RSC Adv. 2021 Dec 14;11(63):39781-39789. doi: 10.1039/d1ra08377e. eCollection 2021 Dec 13.

Authors

Hao-Wei Chen^{1

2}, Chun-Xiao Jiang^{1

2}, Jiyang Li¹, Na Li², Yi Zang³, Xi-Ying Wu^{1

4}, Wen-Xue Chen⁵, Juan Xiong¹, Jia Li³, Jin-Feng Hu^{1

2}

Affiliations

¹ Department of Natural Medicine, School of Pharmacy, Fudan University Shanghai 201203 PR China jxiong@fudan.edu.cn jfhu@fudan.edu.cn.
² School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Ecology and Conservation, Taizhou University Zhejiang 318000 PR China jfhu@tzc.edu.cn.
³ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences Shanghai 201203 PR China.
⁴ Shanghai Skin Disease Hospital, School of Medicine, Tongji University Shanghai 200443 PR China.
⁵ Department of Chemistry, Fudan University Shanghai 200438 PR China.

Abstract

A number of previously undescribed (1-7) and structurally related known (8-17) isobenzofuran-type polyketides were obtained from the fermentation of Penicillium commune P-4-1, an endophytic fungus isolated from the fresh trunk bark of the critically endangered conifer Abies beshanzuensis. Beshanzoides A-D (1-4, resp.) feature a cycloheptanone-containing isobenzofuran ring system hitherto unknown, which might be biosynthesized via two steps of aldol reactions starting from a common co-occurring isobenzofuran-type polyketide as the precursor. The new structures were elucidated by spectroscopic methods, electronic circular dichroism data, and single crystal X-ray diffraction analyses. Beshanzoide E (5) showed antimicrobial activity (MIC: 16 μg mL^-1) against Staphylococcus aureus, whereas (±)-strobide A (10) inhibited (MIC: 16 μg mL^-1) Candida albicans. Cyclopaldic acid (12) and 3-O-methyl-cyclopaldic acid (13) exhibited inhibitory effects against acetyl-CoA carboxylase 1 (ACC1) with IC₅₀ values of 0.96 and 11.77 μM, respectively. Compound 12 also inhibited (IC₅₀: 7.56 μM) ATP-citrate lyase (ACL).