24 エリスロマイシン誘導体のO-メチル化における位置選択性について(口頭発表の部)

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Among a number of attempts to improve the biological properties of erythromycin A (1) and B (2). we have reported that 6-O-methylated erythromycin A possesses high acid-stability and pertains strong antibacterial activity. In the present work, the reported contrast about the regioselectivity in the O-methylation of erythromycin derivatives, namely preferential reactions at C11-hydroxy group for erythromycin A derivative 3, and at C6 hydroxy for erythromycin B derivative 4 and 9-oxime of erythromycin A derivative 5, was studied by generating and examining significantly populating conformers using a conformational space search algorithm (CONFLEX3). Global energy minima of model compounds 6-8 have almost the same ring structure which agrees with the X-ray structure of 1. We observe that, in this conformer, C11-OH is less reactive in the O-methylation than C6-OH because the C11-hydroxy proton forms strong intramolecular hydrogen bonds with carbonyl oxygens at C1 and C9, and also with C6-hydroxy oxygen. A new conformation having C11-hydroxy group in sterically accessible position appears only in 6 in significant population. On the other hand, C6 and C12-OH are held in the ring by formation of a hydrogen bond with C9-carbonyl oxygen. Analyzing of predominantly distributed conformers of model compounds, we conclude that the origin of determining the regioselectivity between C6 and C11-hydroxy groups in the O-methylations of erythromycin derivatives lies in the formation and deformation of intramolecular hydrogen bondings in significantly populating conformers.
天然有機化合物討論会の論文
1992-09-10

24 エリスロマイシン誘導体のO-メチル化における位置選択性について(口頭発表の部)

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