摘要
目的深入研究 2′ ,4″ O 二 (三甲基硅 )红霉素A肟 (EMAO)的合成反应。方法通过对反应过程的监测和产品分析 ,考察溶剂、硅烷化试剂、催化剂对反应的影响 ,研究Z、E异构体的反应活性。结果反应可在室温下进行 ,CH3 CN作溶剂最好 ,用量是EMAO的 5～ 6倍 (体积与质量比 ) ;硅烷化试剂HMDS为EMAO的 3倍摩尔质量较好 ;催化剂Py·HCl和NH4Cl分别为EMAO的 0 3～ 0 5倍和 1 2～ 1 5倍摩尔质量较好。产品收率达 95 % ,纯度达 90 %。结论EMAO的 2′、4″位的两个羟基硅烷化反应是分步进行的 ,反应活性E EMAO大于Z EMAO。
Aim To investigate the synthesis of 2′,4″-O-bis(trimethylsilyl)erythromycin A oxime.Method The influence of the solvent,silylating reagent and catalyzer to the reaction was probed under the inspection of the reactive process and analysis of products.The reactivity of Z,E isomer was detected.Result The reaction can be carried out under room temperature in the best solvent CH_3CN with a 5～6 times of EMAO(volume∶mass).The best mol.ratio between HMDS and EMAO is n(EMAO)∶n(HMDS)=1∶3;catalyzer can be Py·HCl,NH_4Cl or HCO_2H,better mol.ratios the are n(Py·HCl)∶n(EMAO)=1∶0.3～0.5 and n(NH_4Cl)∶n(EMAO)=1∶1.2～1.5.The structure of the product was identified.The yield and purity of the product reached more than 95% and 90%.Conclusion The silylating reaction is not proceeding together at 2′,4″-hydroxyl position and the reactivity of E-EMAO is better than that of Z-EMAO.The yield and purity show a significant improvement by using optimized synthetic reactive conditions.
出处
《中国药物化学杂志》
CAS
CSCD
2004年第3期150-153,共4页
Chinese Journal of Medicinal Chemistry
基金
国家经贸委技术创新基金 (0 1BK - 0 0 9)
河北师范大学青年基金 (2 0 0 2 0 8)
