C(3)-酯基取代的1,5-苯并硫氮杂卓的合成、晶体结构及抑菌和构效关系的研究

设计、合成了三类C(3)酯基取代的1,5-苯并硫氮杂卓衍生物: 2,3/2,5-二氢和2,3,4,5-四氢-1,5-苯并硫氮杂卓-3-甲酸乙酯, 采用元素分析、IR、MS、1H NMR及X射线衍射法确定了标题化合物的分子结构．结构分析表明, 2,5-二氢-1,5-苯并硫氮杂卓-3-甲酸乙酯属单斜晶系, C2/c空间群, 晶胞参数为: a＝2.0319(4) nm, b＝1.4985(3) nm, c＝1.3659(3) nm, α＝90°, β＝120.49(3)°, γ＝90°, V＝3.5840(12) nm3, Z＝8, Dc＝1.397 g/cm3, μ＝0.351 mm－1, F(000)＝1560, R＝0.0478, Rw＝0.1304; 研究了2,3/2,5-二氢-1,5-苯并硫氮杂卓的合成反应条件, 发现该两种互变异构体分别是速度控制产物和平衡控制产物; 抑菌活性及抑真菌构效关系研究表明, 亚胺型的2,3-二氢-1,5-苯并硫氮杂卓具有明显的抑菌活性, 亚胺官能团是其抑真菌的药效团．

Synthesis, Crystal Structure, Antimicrobial Activity and Structure Activity Relationship of 3-Ethoxycarbonyl-1,5-benzothiazepines

Three kinds of 3-ethoxycarbonyl-1,5-benzothiazepines were designed,synthesized and structurally confirmed by elemental analysis,IR,~1H NMR,MS and X-ray diffraction.The crystal of compound 5b belongs to monoclinic,space group C2/c with unit cell dimensions a=2.0319(4)nm,b=1.4985(3)nm,c=1.3659(3)nm,a=90°,β=120.49(3)°,γ=90°,V=3.5840(12)am~3,Z=8,D_c=1.397 g/cm~3,μ=0.351 mm~(-1),F(000)=1560,R=0.0478,and Rw=0.1304.Studies on the synthesis conditions of 2,3/2,5-dihydro-1,5-benzothiazepines revealed that 2,3/2,5-dihydro-1,5-benzothiazepines that are imine-enamine tautomers were speed control and balance conffol products respectively.The biological evaluation of those compounds showed that 1,5-benzothiazepines with C=N group had moderate to excellent antimicrobial activities and the C=N double bond in the newly synthesized compounds was the key function group for their antifungal activities.