摘要
目的 在微机上寻找一种简单易行的方法预测红霉素类化合物甲基化反应中出现的区域选择性。方法用HyperchemPro 6 0软件中构象搜寻模块 (MM +力场 ) ,对红霉素类化合物 4～ 6进行构象搜索 ,寻找低能分子最低能量构象簇 ,对得到的二面角参数进行分类统计分析。结果 考察分类后的构象数和活性基团的位置 ,能预测红霉素类化合物活性基团甲基化反应中的选择性。
Aim In order to find a way to prognosticate the region selectivity in the O methylation reaction of erythromycin and its derivatives, conformation search model of Hyperchem Pro 6 0 used in personal computer was used to establish it. Methods The results of O methylation reaction of compound 1, 2 and 3 showed the difference between 6 OH and 11 OH. Using the conformational search model of hyperchem, 1 000 conformations of compound 4, 5 and 6 were found with the parameter of dihedral angle. The 14 membered lactone ring was defined as a “plane”. The position of carbonyl of 1 or 9 and hydroxyl of 6 or 11 is different, either “up plane” or “down plane”. A statistic analysis of low energy conformation clusters was used to sort these clusters by the parameter of the dihedral angle. The data is in accord with the results of the experiments. Results Conformation numbers, energy minimum, energy average and position of the active groups of compounds 4, 5 and 6, the simplified structures of compound 1, 2 and 3, were given in Table 1. by sorting the dihedral angle. Conclusion The interaction of the hydroxyl and carbonyl were analysed and found that O methylation reactions of erythromycin and its derivatives were impacted by the space factor. The clusters of energy minimum, maximum number and “outside” were discussed. The selectivity of the O methylation reaction of erythromycin and its derivatives can be prognosticated by analysing the parameter of the dihedral angle.
出处
《药学学报》
CAS
CSCD
北大核心
2003年第2期108-112,共5页
Acta Pharmaceutica Sinica
