青霉烯类β-内酰胺抗生素构效关系的理论研究

THEORETICAL STUDIES ON STRUCTURE-ACTIVITY RELATIONSHIP OF β-LACTAM ANTIBIOTICS OF PENEMS

分子力学和分子轨道方法计算表明青霉烯类β-内酰胺抗生素:(1)Penem,(2)△~2-Carpenem,(3)△~1-Carpenem,(4)5s-Penem分子内的张力主要是由于β-内酰胺四员环的键角严重偏离自然值和酰胺氮原子的非平面引起的;(3)的非活性是由于其母核结构特点所致。由我们的计算结果可以认为青霉烯类β-内酰胺抗生素与酶作用的过程要经过内酰胺羰基碳原子的sp^3杂化的过渡状态。

The calculations about some β-lactam antibiotics of penems:(l)penem, (2)△~2-carpenem, (3)△~1-carpenem and (4) 5s-penem have been made with molecular mechanics and molecular orbital calculation methods in this paper. The results showed that the tension in their molecules is due to that the figures of bond angles in the 4 member ring of β-lactam are far from the figures in normal state and the non-planity of β-lactam nitrogen atom. As the result of structral character, (3) is inactivity. Based on our calculation, it can be considered that the process for the reaction between the β-lactam antibiotics of penems and ezyme undergos a transition state that the carbonyl carbon atom is sp^3 hybridized.