(S)-5-乙酰胺甲基-3-[(3-氯-4-取代胺甲基)苯基]-2-噁唑烷酮的合成及抗菌活性

Synthesis and Antibacterial Activity of(S)-5-Acetamidomethyl-3-[(3-chloro-4-substituted aminomethyl)phenyl]-2-oxazolidinones

3-氯-4-甲基苯胺经氯甲酸苄酯酰化、与(R)-正丁酸缩水甘油酯环合、甲磺酰化、叠氮化、叠氮还原成胺、氨基乙酰化、苄位溴化得(S)-5-乙酰胺甲基-3-[(3-氯-4-溴甲基)苯基]-2-噁唑烷酮(Ⅷ),后者与胺类化合物进行取代反应生成(S)-5-乙酰胺甲基-3-[(3-氯-4-取代胺甲基)苯基]-2-噁唑烷酮。35个新化合物的结构经1HNMR、元素分析或MS确证,并测定了它们的体外抗菌活性,发现化合物I13对金葡菌和表葡菌的活性与吗啉噁酮相当。I1和I13对肠球菌的活性优于诺氟沙星。

3-Chloro-4-methylaniline was acylated with benzyl chloroforrnate, followed by cyclization with （R）-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NAN3, reduction with P （OMe）3 and HC1, acylation with Ac20, and bromination with NBS to form （S） -5-acetamidomethyl-3- [ （3-chloro-4- bromomethyl） phenyl]-2-oxazolidinone （Ⅷ）, which was subjected to substitution with various aliphatic and aromatic amines to provide the target compounds 11-135. The structures of 35 new targets were confirmed by ^1HNMR and 25 elemental analyses or MS and some physical constants such as [α]D^25 were reported, too. The results of the in vitro antibacterial activities test against 20 bacteria showed that compound 113 had the effect comparable to that of linezolid against both Staphylococcus aureus and Staphylococcus epidermidis, 11 and 113 had the better activity than norfloxaein against Streptococus enteritidis.