Regioselective synthesis mechanism and crystal structure of 2',4″-0-bis(trimethylsilyl)-6-O-methylerythromycin A 9-O-(1-methoxycyclohexyl) oxime

2',4″-0-bis(trimethylsilyl) 6-0-methylerythromycin A 9-0-(1-methoxycyclohexyl) oxime was regioselectively synthesized and characterized and its crystal structure was determined by the single crystal X-ray structure analysis. The crystal belonged to tetragonal system with 74 space group and a = b = 2.9720(4) nm, c = 1.4939(3) nm, V = 13.195(4) nm³, Z = 8, R = 0.0587, wR = 0.1263, S = 1.004 for 11526 unique reflections. The crystal structure shows that the attack of methylation reagents was blocked by 9-oxime ether as result, a hydrogen bond formed between 11-OH and nitrogen of 9-oxime, and the attack of methylation reagents was blocked by 9-oxime ether, whereas the orientation of 6-OCH₃ was located in the cave surrounded by several rings so that 6-OH was unique one to be exposed to methylation reagents. However, the congestion around 11-OH was loosened, which resulted from the orientation of protective group so that much 6,11-O-dim-ethyl product was yielded. Additionally, the crystal structure of 2',4″-O-bis(trimethylsilyl) erythromycin A 9-0-(1-methoxy-l-methylethyl) oxime was first disclosed as a comparison.