(9S)-12-亚甲基红霉素衍生物的合成及体外抗菌活性  

Synthesis of derivatives of (9S)-12-methylene erythromycin and their antibacterial activity in vitro

作　　者：刘露[1] 杨瑶[1] 施阳[1] 许蓬[1] 雷平生[1] 

机构地区：[1]中国医学科学院,协和医科大学药物研究所新药开发室,北京100050

出　　处：《药学学报》2005年第5期423-427,共5页Acta Pharmaceutica Sinica

摘　　要：目的　合成新的具有抗菌活性的红霉素衍生物。方法　以红霉素为原料,合成中间体2′O, 4″O 二苯甲酰基-(9S)-9-O, 11-O-异丙基-12-亚甲基红霉素与6, 7 去氢-2′-O,-4″-O-二苯甲酰基-(9S)-9-O, 11-O 异丙基12-亚甲基红霉素,进而合成相应(9S) 9 O, 11-O-亚乙基-12-亚甲基衍生物。产物结构经13CNMR,FAB MS确证。对所得化合物进行体外抗菌活性测定。结果　制备11个红霉素衍生物,其中5个未见文献报道。化合物9和12进行了体外抗菌活性测定。结论　化合物9和12表现出较弱的抗菌活性。Aim To synthesizs of derivatives of (9S)-12-methylene erythromycin possessed potent antibacterial activity. Methods Using erythromycin A as a starting material,via two intermediate compounds protected 12,21-dehydroerythromycin A and 6,7∶12,21-didehydro erythromycin A, several 9-O,11-O-ethylidene compounds were obtained. During this process, benzyl and isopropyl have been selected as the protecting group. The structures of compounds obtained were confirmed with ^(13)C NMR and MS-FAB. Their antibacterial activity in vitro was tested. Results Eleven derivatives of erythromycin were synthesized. Five of them were unknown compounds. Conclusion The preliminary biological test showed that two target compounds exhibited less potent antibacterial activity in vitro.

关 键 词：(9S)-9-O 11-O-亚乙基-12-亚甲基红霉素衍生物 合成 抗菌活性 

分 类 号：R915.11[医药卫生—微生物与生化药学]