2',4"-O-双(三甲基硅)红霉素A 9-O-(1-乙氧基-1-甲基乙基)肟的区域选择性甲基化

一锅煮合成并表征了2',4"-O-双(三甲基硅)红霉素A 9-O-(1-乙氧基-1-甲基乙基)肟, 首次在丙酮-水混合溶剂中培养出了单晶. X射线衍射表明, 其结构为四方晶系, I4空间群, 晶胞参数: a＝b＝2.9536(1) nm, c＝1.4488(1) nm, V＝12.63897(4) nm³, Z＝8, R＝0.068, wR＝0.067. 对区域选择性影响因素的研究表明: 甲基化时溶液浓度应控制0.052 mol/L和0.067 mol/L之间; 分别采用了四氢呋喃、二氯甲烷、甲基叔丁基醚、甲苯与二甲亚砜作为混合溶剂进行甲基化反应, 发现在甲苯-二甲亚砜中的效果最好, 6-OH的甲基化选择性可达到81.69%.

Regioselective Methylation of 2',4"-O-Bis(trimethylsilyl)erythromycin A 9-O-(1-Ethoxy-1-methylethyl)oxime

2',4"-O-Bis(trimethylsilyl)erythromycin A 9-O-(1-ethoxy-1-methylethyl)oxime was synthesized in one pot and characterized. The crystal structure of the title compound grown from acetone-water was determined by the single crystal X-ray structure analysis. The crystal belongs to tetragonal system with I4 space group and a＝b＝2.9536(1) nm, c＝1.4488(1) nm, V＝12.63897(4) nm³, Z＝8, R＝0.068, wR＝0.067 for 7266 unique reflections. The research on the regioselectivity has shown that the concentration should be confined within 0.052～0.067 mol/L. Among the candidates of CH₂Cl₂-DMSO, methyl t-butyl ether-DMSO and toluene-DMSO, toluene-DMSO was the best mixture solvent for methylation with 81.69% selectivity to 6-OH, instead of the original expensive THF-DMSO.