Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (10): 2752-2762.DOI: 10.6023/cjoc201705002 Previous Articles     Next Articles


海洋来源真菌Penicillium brevicompactum OUCMDZ-4920的活性产物研究

陈玲玲a, 朱统汉a, 朱国良a, 刘云龙a, 王聪a, Pawinee Piyachaturawatb, Arthit Chairoungduab, 朱伟明a   

  1. a 中国海洋大学医药学院 海洋药物教育部重点实验室 青岛 266003;
    b 玛希隆大学理学院生理学系 曼谷 10400
  • 收稿日期:2017-05-02 修回日期:2017-05-30 发布日期:2017-06-02
  • 通讯作者: 朱伟明
  • 基金资助:


Bioactive Natural Products from the Marine-Derived Penicillium brevicompactum OUCMDZ-4920

Chen Linglinga, Zhu Tonghana, Zhu Guolianga, Liu Yunlonga, Wang Conga, Piyachaturawat Pawineeb, Chairoungdua Arthitb, Zhu Weiminga   

  1. a Key Laboratory of Marine Drugs of Ministry Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003;
    b Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400
  • Received:2017-05-02 Revised:2017-05-30 Published:2017-06-02
  • Contact: 10.6023/cjoc201705002
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos.81561148012,41376148) and the National Natural Science Foundation of Chi-na-Guangdong Fund Joint Project (No.U1501221).

A mycophenolic acid producing strain OUCMDZ-4920, identified as Penicillium brevicompactum, was isolated from a marine sediment (-68 m) collected in South China Sea by means of intergrated chemical and bioactive screening method. Eleven compounds including mycophenolic acid (3) and its seven analogues (1, 2 and 4~8) were isolated from a nutrient-poor fermentation broth of P. brevicompactum OUCMDZ-4920, among which (±)-brevicolides A (1) and B (2) were new compounds. On the bases of spectroscopic and electronic circular dichroism (ECD) analyses, chemical transformation, chiral separation and Mosher's method, new compounds (-)-brevicolide A (1a), (+)-brevicolide A (1b), (-)-brevicolide B (2a) and (+)-brevicolide B (2b) were identified as 7-hydroxy-6-((S)-2-hydroxy-2-((R)-2-methyl-5-oxotetrahydrofuran-2-yl)ethyl)-5-methoxy-4-methylisobenzofuran-1(3H)-one, 7-hydroxy-6-((R)-2-hydroxy-2-((S)-2-methyl-5-oxotetrahydrofuran-2-yl)ethyl)-5-methoxy-4-methylisobenzofuran-1(3H)-one, 7-hydroxy-6-((S)-2-hydroxy-2-((S)-2-methyl-5-oxotetrahydrofuran-2-yl)ethyl)-5-methoxy-4-methylisobenzo-furan-1(3H)-one and 7-hydroxy-6-((R)-2-hydroxy-2-((R)-2-methyl-5-oxotetrahydro-furan-2-yl)ethyl)-5-methoxy-4-methylisobenzo-furan-1(3H)-one, respectively. And the known compounds were identified as mycophenolic acid (3), 3-hydroxymycophenolic acid (4), (S)-4-(5-hydroxy-7-methoxy-4-methyl-1-oxo-1,3-dihydroisobenzo-furan-6-yl)-2-methylbutanoic acid (5), norpestaphthalides A (6) and B (7), 5,7-dihydroxy-4-methylisobenzofuran-1(3H)-one (8), 6,8-dihydroxy-3-(hydroxymethyl)-1H-isochromen-1-one (9), brevianamides A (10) and E (11), respectively. Compound 3 displayed good cytotoxicities against murine leukemia P388 cell, human oral epithelial carcinoma KB cell, human colorectal cancer HT29 cell, human breast cancer MCF-7 cell, and human lung cancer A549 cell as well as good antifungal activity against Candida albicans with the IC50 values of 0.4~5.29 μmol·L-1, and a half maximal inhibitory concentration (MIC) value of 4.7 μmol·L-1, respectively. In addition, four new compounds, (-)-7-O-methylbrevicolide A (12a), (+)-7-O-methyl-brevicolide A (12b), (-)-7-O-methyl-brevicolide B (13a) and (+)-7-O-methylbrevicolide B (13b) were also synthesized.

Key words: marine fungi, Penicillium brevicompactum, mycophenolic acid analogues, cytotoxicity, antifungal activity