在青霉素上立体选择引入6α-甲(烷)氧基的新方法

A Novel Stereoselective Method for the Introduction of a Methoxy (alkoxy) Group into the 6 α-Position of Penicillins

自1971年发现具有7α-甲氧基的Cepha-mycin C及随后半合成的Cefoxitin都耐β-内酰胺酶并对阴性菌作用显著之后,许多化学工作者都注意研究在头孢菌素的7α位及青霉素的6α位上引入甲氧基的有效方法。迄今文献报道的在头孢菌素(青霉素)的7(6)α位引入甲氧基的方法可归纳为阴离子法,重氮物分解法及活化亚胺法。出于青霉素比头孢菌素更敏感,所以反应条件应尽可能温和以避免分解提高收率。我们存合成6α-甲(烷)氧基-6β-取代腙-青霉素时。

6 α-Methoxy (alkoxy)-6 β-hydrazono-penicilins were synthesized by a novel gener- al method to introduce a methoxy (alkoxy) group into the 6 α-position of penicillin. The reaction of the 6-hydrazono-penicillin and aromatic aldehydes in lower alcoholic (C_1-C_3) solvents, was catalyzed by protic acid at room temperature to form 6-ar0matie substituted- azinopenicillins. The nucleophilic attack of the corresponding alkoxy group (C_1-C_3) on C-6 took place simultaneonsly in case of aldehydes with strongly negative nitro groups.