海洋来源真菌Penicillium brevicompactum OUCMDZ-4920的活性产物研究
收稿日期: 2017-05-02
修回日期: 2017-05-30
网络出版日期: 2017-06-02
基金资助
国家自然科学基金（Nos.81561148012&41376148）、国家自然科学基金-广东联合基金（No.U1501221）资助项目
Bioactive Natural Products from the Marine-Derived Penicillium brevicompactum OUCMDZ-4920
Received date: 2017-05-02
Revised date: 2017-05-30
Online published: 2017-06-02
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).
通过化学与生物活性相结合的集成筛选方法，从海底沉积物样品（-68 m）中分离得到一株霉酚酸的产生菌短密青霉菌（Penicillium brevicBompactum OUCMDZ-4920）.从其寡营养发酵产物中分离获得了包括8个霉酚酸类化合物在内的11个化合物，其中外消旋的brevicolides A（1）和B（2）为新化合物.通过光谱分析、电子圆二色谱（ECD）、化学转化、手性拆分和Mosher反应，将其结构依次鉴定为（2'S，3'R）-（-）-brevicolide A（1a）、（2'R，3'S）-（+）-brevicolide A（1b）、（2'S，3'S）-（-）-brevicolide B（2a）、（2'R，3'R）-（+）-brevicolide B（2b）、霉酚酸（3）、3-羟基霉酚酸（4）、（S）-2-甲基-4-[5-羟基-7-甲氧基-4-甲基-1-氧亚基-6-（1，3-二氢异苯并呋喃基）]丁酸（5）、norpestaphthalides A（6）和B（7）、5，7-二甲氧基-4-甲基异苯并呋喃-1（3H）-酮（8）、6，8-二羟基-3-羟甲基-1H-异苯并吡喃-1-酮（9）、brevianamides A（10）和E（11）.化合物3对小鼠白血病细胞P388、人口腔上皮癌细胞KB、人结直肠癌细胞HT29、人乳腺癌细胞MCF-7和人肺癌细胞A549表现出较好的抑制活性，IC50值为0.4~5.29 μmol·L-1，对白色念珠菌表现出较好的抗真菌活性，最小抑菌浓度（MIC）为4.7 μmol·L-1.合成了4个新化合物（-）-7-O-methylbrevicolide A（12a）、（+）-7-O-methylbrevicolide A（12b）、（-）-7-O-methyl-brevicolide B（13a）和（+）-7-O-methylbrevicolide B（13b）.
陈玲玲 , 朱统汉 , 朱国良 , 刘云龙 , 王聪 , Pawinee Piyachaturawat , Arthit Chairoungdua , 朱伟明 . 海洋来源真菌Penicillium brevicompactum OUCMDZ-4920的活性产物研究[J]. 有机化学, 2017 , 37(10) : 2752 -2762 . DOI: 10.6023/cjoc201705002
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.
[1] Zhao, C.-Y.; Zhu, T.-H.; Zhu, W.-M. Chin. J. Org. Chem. 2013, 33, 1195(in Chinese). (赵成英, 朱统汉, 朱伟明, 有机化学, 2013, 33, 1195.)
[2] Ma, H.-G.; Liu, Q.; Zhu, G.-L.; Liu, H.-S.; Zhu, W.-M. J. Asian Nat. Prod. Res. 2016, 18, 92.
[3] Regina, S.; Christina, B.; Alban, R.; Jens, H. ISME J. 2010, 4, 159.
[4] Jekkel, A.; Barta, I.; Boros, S.; Süt?, J.; Horváth, G.; Szabó, Z.; Ambrus, G. J. Mol. Catal. B:Enzym. 2002, 19~20, 209.
[5] Habib, E.; León, F.; Bauer, J. D.; Hill, R. A.; Carvalho, P.; Cutler, H. G.; Cutler, S. J. J. Nat. Prod. 2008, 71, 1915.
[6] Hemphill, C. F. P.; Daletos, G.; Liu, Z.; Lin, W.-H.; Proksch, P. Tetrahedron Lett. 2016, 57, 2078.
[7] Kumagai, H.; Amemiya, M.; Naganawa, H.; Sawa, T.; Ishizuka, M.; Takeuchi, T. J. Antibiot. 1994, 47, 440.
[8] Williams, R. M.; Kwast, E.; Coffman, H.; Glinka, T. J. Am. Chem. Soc. 1989, 111, 3064.
[9] Jia, Y.-L.; Guan, F.-F.; Ma, J.; Wang, C.-Y.; Shao, C.-L. Chin. J. Mar. Drugs 2016, 35, 35(in Chinese). (贾彦来, 管菲菲, 马洁, 王长云, 邵长伦, 中国海洋药物, 2016, 35, 35.)
[10] Kato, H.; Nakamura, Y.; Finefield, J. M.; Umaoka, H.; Nakahara, T.; Williams, R. M.; Tsukamoto, S. Tetrahedron Lett. 2011, 52, 6923.
[11] Kato, H.; Nakamura, Y.; Finefield, J. M.; Umaoka, H.; Nakahara, T.; Williams, R. M.; Tsukamoto, S. Tetrahedron Lett. 2014, 55, 559.
[12] Lu, X.-H.; Zheng, Z.-H.; Zhang, H.; Huo, C.-H.; Dong, Y.-S.; Ma, Y.; Ren, X.; Ke, A.-B.; He, J.-G.; Gu, Y.-C.; Shi, Q.-W. J. Antibiot. 2009, 62, 527.
[13] Campbell, I. M.; Calzadilla, C. H.; McCorkindale, N. J. Tetrahedron Lett. 1966, 42, 5107.
[14] Allison, A. C.; Eugui, E. M. Clin. Transplant. 1993, 7, 96.
[15] Bentley, R. Chem. Rev. 2000, 100, 3801.
[16] Chen, Z.; Zheng, Z.; Huang, H.; Song, Y.; Zhang, X.; Ma, J.; Wang, B.; Zhang, C.; Ju, J. Bioorg. Med. Chem. Lett. 2012, 22, 3332.
[17] Jones, D. F.; Moore, R. H.; Crawley, G. C. J. Chem. Soc. C 1970, 12, 1725.
[18] Uchida, K.; Watanabe, H.; Usui, T.; Osada, H.; Kitahara, T. Heterocycles 1998, 48, 2049.
[19] Fujimoto, H.; Fujimaki, T.; Okuyama, E.; Yamazaki, M. Chem. Pharm. Bull. 1999, 47, 1426.
[20] Ayer, W. A.; Browne, L. M.; Feng, M. C.; Orszanska, H.; Saeedighomi, H. Can. J. Chem. 1986, 64, 904.
[21] Birch, A. J.; Wright, J. J. Tetrahedron 1970, 26, 2329.
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