红霉素A9(O-叔丁基二甲基硅)肟的合成

以红霉素A与盐酸羟胺反应得到红霉素A肟(EMAO,Ⅰ),再以叔丁基二甲基氯硅烷(TBDMSC l)与Ⅰ进行硅醚化反应制备红霉素A9(O-叔丁基二甲基硅)肟(TBDS-EMAO,Ⅱ)。研究了硅醚化反应的溶剂化作用,有机碱催化作用,Z、E异构体的活性。实验结果表明,含孤电子对的极性非质子溶剂及相应的有机碱催化剂有助于在含有多个羟基的Ⅰ中进行肟羟基的选择性硅醚化反应。硅醚化反应以THF为溶剂,室温,反应物浓度c(Ⅰ)=0.27~0.53 mol/L,硅醚化试剂用量n(TBDMSC l)∶n(Ⅰ)=1.4∶1,有机碱用量n(Et3N)∶n(Ⅰ)=2.2∶1时,收率可达97%。用HPLC分析了产品及相应的异构体,Z-Ⅱ反应活性较E-Ⅱ高。用IR1、HNMR1、3CNMR、EI-MS以及元素分析确证了相关物质的结构。

Synthesis of Erythromycin A9(O-t-butyldimethylsilyl) Oxime

Erythromycin A reacted with hydroxylamine hydrochloride to form erythromycin A oxime(EMAO,Ⅰ).Then Ⅰ was silylated with tert-butyldimethylsilyl chloride(TBDMSCl) to give erythromycin A 9(O-t-butyldimethylsilyl) oxime(TBDS-EMAO,Ⅱ).The effect of solvent,catalyst,and reactivity of silylating agent toward the Z/E isomers of Ⅱ were studied.The experiment reveals that selective silylation reaction toward Ⅰ containg multiple hydroxyl groups is promoted by polar aprotic solvent and organic base catalyst with unshared pair of electrons.The silylation reaction can be easily performed in THF at room temperature with c(Ⅰ)=0.27～0.53 mol/L,n(TBDMSCl)∶n(Ⅰ)=1.4∶1 and n(Et_3N)∶n(Ⅰ)=2.2∶1 to give Ⅱ in 97% yield.The product and coresponding Z/E isomers were analysized by HPLC,showing that the reactivity of Z-Ⅱ is higher than E-Ⅱ.Their structures were identified by IR,~1HNMR,~(13)CNMR,EI-MS and elementary analysis.