酶催化拆分外消旋药物的研究进展

Research Progress of Enzymatic Resolution of Racemic Drugs

外消旋药物中通常存在不同的对映异构体,但在药物中往往只有一种对映体才具有实际的疗效,这不仅可以排除由于无效(不良)对映体所引起的毒副作用,还能减少药物剂量和人体对无效对映体的代谢负担,对药物动力学及剂量有更好的控制,提高药物的专一性。脂肪酶作为一种特殊有效的生物酶催化剂,利用其高度立体选择性将外消旋体拆分成单一光学异构体,底物转化率和对映体选择性较高,反应条件温和且副反应较少。文章对酶催化拆分外消旋化合物的现状和影响因素进行了综述。

Different enantiomers are usually present in racemic drugs,but there is often only one enantiomer in the drug to have a practical effect,which not only eliminates the side effects caused by the ineffective(bad)enantiomers.It can also reduce the drug dosage and the metabolic burden of the inactive enantiomers,better control of pharmacokinetics and dosage,and improve drug specificity.As a special and effective bio-enzyme catalyst,lipase utilizes its high stereoselectivity to resolution the racemates into a single optical isomer,with higher substrate conversion and enantioselectivity,mild reaction conditions and less byproducts.In this paper,the current status and influencing factors of enzymatic resolution of racemic compounds were reviewed.