MODIFICATION OF MACROLIDE ANTIBIOTICS - SYNTHESIS OF 11-DEOXY-11-(CARBOXYAMINO)-6-O-METHYLERYTHROMYCIN-A 11,12-(CYCLIC ESTERS) VIA AN INTRAMOLECULAR MICHAEL REACTION OF O-CARBAMATES WITH AN ALPHA,BETA-UNSATURATED KETONE
MODIFICATION OF MACROLIDE ANTIBIOTICS - SYNTHESIS OF 11-DEOXY-11-(CARBOXYAMINO)-6-O-METHYLERYTHROMYCIN-A 11,12-(CYCLIC ESTERS) VIA AN INTRAMOLECULAR MICHAEL REACTION OF O-CARBAMATES WITH AN ALPHA,BETA-UNSATURATED KETONE
复制标题
DOI：
10.1021/jo00245a038
复制
发表时间：
1988-05-13
影响因子：
3.6
通讯作者：
KIM, KH
中科院分区：
文献类型：
--
作者：
BAKER, WR;CLARK, JD;KIM, KH
以6-O-甲基红霉素A为原料，经五步反应合成11-脱氧-11-羧氨基-6-O-甲基红霉素A11，12-（环酯）13，总收率40%。该方法的特征在于C-12 O-氨基甲酸酯与α，贝塔不饱和酮Michael反应需要碱催化，并且在极性溶剂如10%乙腈水溶液或二甲基甲酰胺中加成速率最快。关键中间体酰基咪唑11 a与伯胺反应，在一次操作中产生环状11，12-氨基甲酸酯。产物氨基甲酸酯的立体化学通过最小能量计算、二维NMR光谱技术和13 C NMR相关性来确定。
The synthesis of 11-deoxy-11-(carboxyamino)-6-O-methylerythromycin A 11,12-(cyclic esters) 13 was accomplished in five steps with 6-O-methylerythromycin A in 40% overall yield. The process featured a mild and stereoselective intramolecular Michael addition of C-12 O-carbamates to an .alpha.,.beta.-unsaturated ketone. The Michael reaction required base catalysis and the rate of addition was fastest in polar solvents such as 10% aqueous acetonitrile or dimethylformamide. Reaction of the key intermediate acyl imidazole 11a with primary amines produced in one operation the cyclic 11,12-carbamates. The stereochemistry of the product carbamates was determined by minimum energy calculations, two-dimensional NMR spectroscopic techniques, and 13C NMR correlations.