摘要
目的研究噁唑烷酮类衍生物的合成及抗菌活性。方法以4-甲基-3-卤代苯胺为原料,经氯甲酸苄酯酰化、与(R)-丁酸缩水甘油酯环合、甲磺酰化、叠氮化、叠氮还原成胺、胺基乙酰化、苄位溴化得到中间体取代溴苄V IIIa和V IIIb。V IIIa和V IIIb与胺类化合物包括脂肪胺、芳香胺发生取代反应生成IX a和IX b;测定目标化合物的体外抗菌活性。结果设计、合成了51个新化合物,其结构经1H NMR、元素分析或MS确证。并测定了它们的比旋光度等理化常数。化合物V IIb,IX a1,IX a2,IX a7,IX b1,IX b3,IX b10,IX b16和IX b23对G+菌有一定的活性,但不如对照品吗啉噁酮和诺氟沙星。结论在吗啉噁酮结构中苯环4位和吗啉基之间插入亚甲基,不能提高化合物的抗菌活性。
Aim To synthesize oxazolindinone derivatives and test their antibacterial activities. Methods 3-Halo-4-methylaniline was acylated with benzyl chloroformate, followed by cyclization with （R）-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NaN3, reduction with H2 ＋ Pd/C or P（OMe）3 ＋ HCl, acylation with Ac2O, and bromination with NBS to form bromides Ⅷa and ⅧⅨb, Substitution of the bromides with various amines including aliphatic amine and aromatic amine provided the target compounds Ⅸa and Ⅸb. The in vitro antibacterial activity of the target compounds was tested. Results Fifty one new compounds were designed and synthesized. And their structures were confirmed by ^1H NMR and elemental analyses or MS. Some physical constants such as [α]D^25 were reported also. Compounds VIIb, Ⅸa1, Ⅸa2, Ⅸa7, Ⅸb1, Ⅸb3, Ⅸb10, Ⅸb16 and Ⅸb23 had moderate in vitro antibacterial activity against G^＋ bacteria but they were less active than linezolid or norfloxacin. Conclusion Insertion of methylene group between 4-position of phenyl and morpholinyl group in linezolid derivatives can not increase the antibacterial activity.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第5期418-425,共8页
Acta Pharmaceutica Sinica
基金
上海市科委资助项目(04JC14068
04DZ05902).
关键词
噁唑烷酮衍生物
吗啉噁酮
抗菌活性
oxazolindinone derivatives
linezolid
antibacterial activity
