【摘要】 以(R)/(S)-4-苄基-2-噁唑烷酮为手性助剂,采用不对称合成方法制备了18个具有光学活性的2-甲氧羰基-4-氟苯基-1,5-苯并硫氮杂卓类化合物9a~9i和14a~14i,经HPLC分析e.e.值较为理想;通过核磁共振谱、红外光谱和高分辨质谱表征了其结构,通过单晶X射线衍射法确定化合物9h的相对构型;用抑菌圈法测试了目标化合物对新生隐球菌的抑菌活性.研究结果表明,由S型手性助剂诱导不对称合成的杂卓对新生隐球菌的抑制作用普遍高于由R型手性助剂诱导合成的杂卓及外消旋体.测试了抑菌活性较好的化合物14a~14f的最小抑菌浓度(MIC)和最小杀菌浓度(MFC),发现其对新生隐球菌的MIC和MFC均低于抗真菌药物氟康唑.更多还原

【Abstract】 The synthetic route was confirmed via the study of introduction or removing chiral auxiliary（ R）-4-phenyl-2-oxazolidinone and optimizing reaction conditions. Eighteen optically active 1,5-benzothiazepines were synthesized under the chiral induction of（ S） /（ R）-4-benzyl-2-oxazolidinone and characterized by ¹H NMR,¹³C NMR,IR and HRMS. The relative configuration of compound 9h was validated by X-ray diffraction analysis. The e. e. values of the products were analyzed by HPLC. The antifungal activities of compounds were screened using the disk diffusion method against C. neoformans. The compounds which were synthesized with S-4-benzyl-2-oxazolidinone had high antibacterial effects against C. Neoformans. By contrast,the compounds which were synthesized with R-4-benzyl-2-oxazolidinone and racemic compounds had lower antibacterial effects. Moreover,The MIC and MFC values of the highly biological compounds 14a—14f were lower than those of fluconazole.更多还原