Duran Dilek, Aviyente Viktorya, Baysal Canan
Chemistry Department, Faculty of Art and Sciences, Boğaziçi University, Bebek, 34342 Istanbul, Turkey.
J Mol Model. 2004 Apr;10(2):94-101. doi: 10.1007/s00894-003-0172-7. Epub 2004 Jan 13.
Dirithromycin is a macrolide antibiotic derived from erythromycin A. Dirithromycin is synthesized by the condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)-acetaldehyde. To gain insight into the synthesis, the condensation mechanism has been analyzed computationally by the AM1 method in the gas phase. First, the formation of the Schiff bases of dirithromycin and epidirithromycin from 9(S)-erythromycylamine and 2-(2-methoxyethoxy)-acetaldehyde were modeled. Then, the tautomerization of the Schiff bases to dirithromycin and epidirithromycin were considered. Finally, the epimerization of the Schiff base of epidirithromycin to the Schiff base of dirithromycin was investigated. Our results show that, even though carbinolamine forms faster for epidirithromycin than the corresponding structure for dirithromycin, dirithromycin is the major product of the synthesis.
地红霉素是一种由红霉素A衍生而来的大环内酯类抗生素。地红霉素由9(S)-红霉素胺与2-(2-甲氧基乙氧基)-乙醛缩合而成。为深入了解该合成过程，采用AM1方法在气相中通过计算分析了缩合机理。首先，对9(S)-红霉素胺与2-(2-甲氧基乙氧基)-乙醛形成地红霉素和表地红霉素席夫碱的过程进行了建模。然后，考虑了席夫碱向地红霉素和表地红霉素的互变异构。最后，研究了表地红霉素席夫碱向地红霉素席夫碱的差向异构化。我们的结果表明，尽管表地红霉素的甲醇胺形成速度比地红霉素的相应结构快，但地红霉素是合成的主要产物。
