【作者】 金伟；

【导师】 李桂玲；

【作者基本信息】 华中科技大学 ， 有机化学， 2007， 硕士

【摘要】 环氧-二十碳三烯酸(EETs)在心血管系统中有多种重要的生物学功能,国外学者研究发现14,15-环氧二十碳-5-(Z)-烯酸(14,15-EE-5-ZE)能特异性地拮抗由EET诱导的血管舒张,并且对血管增生具有抑制作用,因此我们推测其能应用于肿瘤的治疗。本文设计了14,15-EE-5-ZE的前体化合物(5,14)-二十碳二炔-1-四氢吡喃醚的合成路线,对其合成进行了详细的研究。以1,7-庚二醇为起始原料,用氢溴酸将其溴代,得到7-溴-1-庚醇。用2,3-二氢吡喃保护7-溴-1-庚醇的羟基,得到7-溴-1-庚醇的四氢吡喃醚,将其与1-庚炔进行偶连,得到8-十四炔-1-四氢吡喃醚。以PPTs为催化剂,脱除8-十四炔-1-四氢吡喃醚的羟基保护基,得到8-十四炔-1-醇。用四溴化碳和三苯基磷作为溴代试剂将8-十四炔-1-醇溴代,得到1-溴-8-十四炔。另外用2,3-二氢吡喃保护5-己炔-1-醇的羟基,得到5-己炔-1-四氢吡喃醚。最后将5-己炔-1-四氢吡喃醚与1-溴-8-十四炔进行偶连,得到产物(5,14)-二十碳二炔-1-四氢吡喃醚。实验总收率14.5%。我们做了如下创新:设计了(5,14)-二十碳二炔-1-四氢吡喃醚新的合成路线;首次研究了1,7-庚二醇的单溴代反应的反应溶剂、反应温度、反应时间、反应物摩尔比等因素对产率的影响;对端位炔烃与溴代烷的偶连反应的无水无氧实验方法进行了设计和改进,缩短了反应时间,使产物易于分离提纯。产物用硅胶柱层析分离提纯,并用红外光谱、氢核磁共振谱及质谱验证了产物的结构。结果表明合成路线完全可行。更多还原

【Abstract】 Cytochrome P-450 metabolites, including the epoxyeicosatrienoic acids (EETs) which play an important role in the system of heart vein. In the recent years, a 14,15-EET analogue, (14,15)-epoxyeicosa-5(Z)-enoic acid (14,15-EE-5-ZE) was synthesized and identified as an EET-specific antagonist. In our work, we designed and researched the synthesis route of a key intermediate (5,14)-eicosadiyne-1-tetrahydropyran and synthesized it.1,7-heptadiol, the starting material, reacted with hydrobromic acid to produce 7-bromheptane-1-ol, which hydroxy was protected by 2,3-dihydropyran . Then, it coupled with the heptaalkyne. The coupling product was taken off the 2,3-dihydropyran at the extremity, and the alcohol we obtained was brominated with CBr4 and PPh3, furnishing a new bromide (a). Next, the hydroxy of 5-hexyne-1-ol was protected by 2,3-dihydropyran with the catalytic reaction of PPTs. Alkylation of the protected alkyne, using bromide (a), produced the bis-acetylene. The total yield was 14.5%.Some innovations we did as following: firstly, we designed a new synthesis route of (5,14)-eicosadiyne-1-tetrahydropyran; secondly, we studied the bromination reaction influence factors of 1,7-heptadiol in detail, including reaction time、reaction temperature、solvent dosage、reagent mole ratio; thirdly, we discussed the mechanism of 1-alkyne coupled with mono-bromide, and optimized the reaction condition.We utilized silica gel column chromatography to separate and purify product, and applied infrared spectrum、1H NMR and mass spectrum to testify product structure. The final result indicated that our synthesis route was feasible.更多还原