【作者】 刘耀红；

【导师】 周乐；

【作者基本信息】 西北农林科技大学 ， 应用化学， 2008， 硕士

【摘要】 天然产物的研究开发一般分为三个层次:（1）天然产物的直接应用,（2）天然产物中活性成分的结构修饰和改造,（3）作为先导化合物,合成筛选出活性更好的化合物,本论文在第二个层次上展开研究。我们以活性优秀的新狼毒素B为研究对象,采用化学修饰法合成了系列新狼毒素B的衍生物,通过测定和评价各修饰物的抑菌活性,揭示了新狼毒素B中各官能团与其抑菌活性的关系。以乙酸酐为乙酰化试剂,合成了A、B、C、D四个乙酰化衍生物。以硫酸二甲酯为甲醚化试剂对n-B进行甲醚化修饰,合成并分离出E、F、G、H四个甲醚化衍生物。以NaBH₄为还原剂,对n-B羰基进行还原,合成出两个单、双羰基还原产物J、K。以盐酸羟胺为肟化剂,合成出n-B的两个单、双肟衍生物。经HPLC,TLC,mp值,R_f值,UV,IR,CI-MS,¹H NMR,¹³C NMR谱图综合解析确定了各衍生物的化学结构:A为7″-乙酰氧基-7,4′,4′″,5,5″-五羟基-3,3″-双二氢黄酮;B为4′,7-二乙酰氧基-4′″,7″,5,5″-四羟基-3,3″-双二氢黄酮;C为4′,7,7″-三乙酰氧基-4′″,5,5″-三羟基-3,3″-双二氢黄酮;D为4′,4′″,7,7″-四乙酰氧基-5,5″-二羟基-3,3″-双二氢黄酮;E为7″-甲氧基-7,4′,4′″,5,5″-五羟基-3,3″-双二氢黄酮;F为7,7″-二甲氧基-4′,4′″,5,5″-四羟基-3,3″-双二氢黄酮;G可能为为7,7″,4′-三甲氧基-4′″,5,5″-三羟基-3,3″-双二氢黄酮和7,7″,4′″-三甲氧基-4′,5,5″-三羟基-3,3″-双二氢黄酮的混合物或其中一种;H为7,7″,4′,4′″-四甲氧基-5,5″-二羟基-3,3″-双二氢黄酮;J为4-脱氧新狼毒素B;K为4-脱氧新狼毒素B和4,4″-二脱氧新狼毒素B的混合物;L为4-新狼毒素B肟或者4′-新狼毒素B肟;M为4,4″-新狼毒素B双肟:W为7,7″,4′,4′″-四苯甲酰基-5,5″-二羟基-3,3″-双二氢黄酮选择鳗弧菌、肠型点状气单胞菌、嗜水气单胞菌、金黄色葡萄球菌和大肠杆菌为供试菌,采用倍比稀释法对n-B及其衍生物、青霉素钠、头孢曲松钠进行了抑菌活性测定。综合分析抑菌活性和结构的关系,可以得出如下结论:n-B分子中6个酚羟基（4′,4′″,7,7″,5和5″酚羟基）中的4′,4′″,7和7″酚羟基部分或全部是其主要活性基团:7和7″酚羟基与n-B抗G^-菌（肠形点状气单胞菌）的活性密切相关;4′和4′″酚羟基与n-B抗G⁺菌的活性有较重要关系;5和5″酚羟基对其抑菌活性贡献不大;n-B的羰基与其抑菌活性没有关系,同时不同位置酚羟基对n-B抑菌活性的贡献因菌而异。更多还原

【Abstract】 There are three strategies to research and develop natural products.Firstly,the rude extracts are used as drugs.Secondly,the active compound is isolated and its derivatives are synthesized.Thirdly,the active compound is used as lead compound to synthesize and screen the new advanced compound.Here we take the second strategy,and study on Neochamaejasmine B which has strong biological activity.Through determination and evaluation antibacterial activity of series of neochamaejasmine B derivatives,the relationship between functional groups and antibacterial activity of neochamaejasmine B was disclosed.Use acetic anhydride as acetylation reagent,compounds A,B,C,D were prepared. Through reaction between neochamaejasmine B and Me₂SO₄,compounds E,F,G,H,were prepared.The single or double carbonyl reduction derivative was prepared Use NaBH₄ as the reductan.Compounds L and M were synthesized through reaction between neochamaejasmine B and NH₂OH.HCL.Based on their spectral data(ESI-MSH,¹N MR and ¹³C NMR),HPLC,mp value and Rf value the compounds were identified as follows:7″-acetoxy-7,4′,4′″,5,5″-pentahydroxy-3,3″-biflavanone,（A）,7,7″-diacetoxy-4′,4′″,5,5″-tetrahydroxy-3,3″-biflavanone,（B）7,7″,4′-triacetoxy-4′″,5,5″-trihydroxy-3,3″-biflavanone,（C）7,7″,4′,4′″-tetracetoxy-5,5″-dihydroxy-3,3″-biflavanone（D）,7″-methoxy-7,4′,4′″,5,5″-pentahydroxy-3,3″-biflavanone（E）,7,7″-dimethoxy-4′,4′″,5,5″-tetrahydroxy-3,3″-biflavanone（F）,7,7″,4′-trime-thoxy-4′″,5,5″-trihydroxy-3,3″-biflavanone and7,7″,4′″-trimethoxy-4′,5,5″-trihydroxy-3,3″-biflavanone（G）,7,7″,4′,4′″-tetramethoxy-5,5″-dihydroxy-3,3″-biflavanone（H）,4-deoxyneochamaejasmine B（J）,4-deoxyneochamaejasmine B or 4,4″-double deoxyneochamaejasmine B（K）,4-neochamaejasmine B oxime or 4′-neochamaejasmine B oxime（L）,4,4″-double neochamaejasmine B oxime（M）,7,7″,4′,4′″-tetrbenzoyl-5,5″-dihydroxy-3, 3″-biflavanone（W）.We choose Vibrio anguillarum,AeromonasPunctat fintestinalis,Aeromonas hydrophila, Staphylococcus aureas and Escherichia coli as tested bacteria;choose penicillin Na and Ceftriaxone Sodium as controls.The antibacterial activity was tested by double dilution method in vitro against tested bacteria.Compared with antibacterial activity of neochamaejasmine B and its derivatives,it was concluded that 7-OH,7″-OH,4′-OH and 4′″-OH of neochamaejasmine B were the main active groups;7-OH and 7″-OH of neochamaejasmine B are closely related to against G^- bacteria（AeromonasPunctat fintestinalis）;4-OH and 4″-OH of neochamaejasmine B are important for against G⁺ bacteria; 5-OH and 5″-OH of neochamaejasmine B have little effect for antibacterial activity;the carbonyl group of neochamaejasmine B shows no biological activity,and the contribution of phenolic hydroxyl for neochamaejasmine B inhibition bacterial is various for diffirent bacteria.更多还原