[Prognosticating the region-selectivity in the O-methylation reaction of erythromycins by conformational search model].
OBJECTIVE
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.


CONCLUSIONS
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.
Xu
Jin
J
China Pharmaceutical University, Nanjing 210009, China.
Lin
Ke-jiang
KJ
You
Qi-dong
QD
D001330:Electronic Data Processing; D004917:Erythromycin / Q000737:chemistry* / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure
D004917:Erythromycin