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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 brevic Bompactum 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0.4~5.29μmol·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4.7μmol·L~(-1).合成了4个新化合物(-)-7-O-methylbrevicolide A(12a)、(+)-7-O-methylbrevicolide A(12b)、(-)-7-O-methylbrevicolide B(13a)和(+)-7-O-methylbrevicolide B(13b).
One mycophenolate-producing strain Penicillium brevic Bompactum OUCMDZ-4920 was isolated from the seabed sediment samples (-68 m) by an integrated screening method combining chemical and biological activities. From its oligotrophic Eleven compounds including eight mycophenolic acids were isolated from fermentation products, among which racemic brevicolides A (1) and B (2) were new compounds.According to spectral analysis, electron circular dichroism ), Chemical transformation, chiral resolution and Mosher reaction, the structures were identified as (2’S, 3’R) - (-) - brevicolide A Brevicolide B (2a), (2’R, 3’R) - (+) - brevicolide B (2b), mycophenolic acid (3), 3- (4), (S) -2-methyl-4- [5-hydroxy-7-methoxy-4-methyl-1-oxo-6- (5), norpestaphthalides A (6) and B (7), 5,7-dimethoxy-4-methylisobenzofuran-1 (3H) ), 6,8-dihydroxy-3-hydroxymethyl-1H-isochromen-1-one (9), brevianamides A (10) and E (11) .Compound 3 inhibited murine leukemia cells P388, Human oral epithelial cancer cells KB, human colorectal cancer Cells HT29, human breast cancer cells MCF-7 and human lung cancer cells A549 showed good inhibitory activity, IC50 value of 0.4 ~ 5.29μmol·L -1, Candida albicans showed good antifungal activity (MIC) was 4.7μmol·L -1, and four new compounds (-) - 7-O-methylbrevicolide A (12a) (-) - 7-O-methylbreicolide B (13a) and (+) - 7-O-methylbreicolide B (13b).