Mordi M N, Pelta M D, Boote V, Morris G A, Barber J
School of Pharmacy, Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, U.K.
J Med Chem. 2000 Feb 10;43(3):467-74. doi: 10.1021/jm9904811.
One of the major drawbacks in the use of the antibiotic erythromycin A is its extreme acid sensitivity, leading to degradation in the stomach following oral administration. The modern derivative clarithromycin degrades by a different mechanism and much more slowly. We have studied the pathway and kinetics of the acid-catalyzed degradation of clarithromycin and of erythromycin B, a biosynthetic precursor of erythromycin A which also has good antibacterial activity, using (1)H NMR spectroscopy. Both drugs degrade by loss of the cladinose sugar ring and with similar rates of reaction. These results suggest that erythromycin B has potential as an independent therapeutic entity, with superior acid stability compared with erythromycin A and with the advantage over clarithromycin of being a natural product.
抗生素红霉素A使用中的一个主要缺点是其对酸极度敏感，口服后会在胃中降解。现代衍生物克拉霉素通过不同的机制降解，且降解速度要慢得多。我们使用核磁共振氢谱研究了克拉霉素以及红霉素B（红霉素A的生物合成前体，也具有良好的抗菌活性）的酸催化降解途径和动力学。两种药物均通过克拉定糖环的丢失而降解，且反应速率相似。这些结果表明，红霉素B有潜力作为一种独立的治疗实体，与红霉素A相比具有更高的酸稳定性，并且相对于克拉霉素的优势在于它是一种天然产物。
