【作者】 郭进；

【导师】 孙良东；

【作者基本信息】 天津大学 ， 有机化学， 2008， 硕士

【摘要】 本论文主要讲述了天然产物楝酰胺(Rocaglamide)类化合物全合成的探索研究。Rocaglamide是King等人首次于1982年从Aglaia elliptica(Meliace)等楝属植物中提取分离并通过X射线衍射方法确定结构的,是一种具有杀虫、抗癌、抗白血病活性的环戊烷苯并呋喃稠三环骨架的化合物。如何立体选择性合成楝酰胺骨架,控制环戊烷上五个手性中心的构型,解决对映选择性较差,产率较低的问题,是当今合成化学家面临的一个挑战。本论文选题正是从这个角度出发,拟采用全新的合成路线来立体选择性的合成几个该类化合物。所设计的合成路线原料价廉易得,合成方法较简单,合成路线较短。该课题拟解决原来合成路线中非对映选择性差的问题,用全新的方法构建环戊烷苯并呋喃骨架,并使环戊烷上五个手性中心的立体构型与楝酰胺相同。首先,由间苯三酚通过Vilsmeier-Hack反应和甲基化反应合成6-羟基-2,4-二甲氧基苯甲醛,再使其与对甲氧基苯丙酮经过HCl气作用下的成盐环化,氧化重排反应得到关键反应中间体4,6-二甲氧基-2-(4’-甲氧基苯基)-3-乙酰基苯并呋喃。从该中间体出发,采用三条路线试图完成楝酰胺类化合物的全合成。路线一经过Adol反应和Knoevenagel等缩合反应成功得到了合成目标产物的两个重要前体化合物。如何通过顺式关环的Nazarov环化反应合成环戊烷的骨架,成为该合成路线的最后一步。经过系统和反复的尝试,得到的多为混合物,且产率较差,难以分辨是否有目标产物的生成,课题组放弃对该路线最后一步的进一步尝试。虽然最后一步没能成功,但是我们积累了一些经验,合成了一些新化合物,对以后的课题研究有一定的意义。路线二采用了简单易得的原料进行了初步探索,较为成功,产率较高,发现了合成2-(4’-甲氧基苯基)苯并呋喃-3-酮较为理想的方法,对关键反应Claisen重排的探索也积累了一定的经验,成功完成最后三步反应的希望很大。路线三中已成功合成1-苯基丙二烯,接下来光催化的[2+2]反应尝试了一些条件,尚未成功,如何找到合适的溶剂和最佳的光照条件来促进该反应的发生和选择性是今后课题研究的重点。更多还原

【Abstract】 The attempted total synthesis of natural product-Rocaglamide and its analogues was described in the dissertation. Isolated from the roots and stems of Aglaia elliptifolia (Meliace), Rocglamide has been proved to be of anti-tumor, anti-leukemic and insecticidal activities. Its structure, determined by single-crystal X-ray analysis, was reported in 1982 by King et. al. It’s a challenge to synthesis of the tricyclic core structure of cyclopenta[b]benzofuran skeleton bearing a highly functionalized cyclopentane moiety with five stereogenic centers. The advantages of our short synthesis route to Rocglamide are utilizing inexpensive reagents, conducting under mild reaction conditions and obtaining the product in high stereoselectivity.First, 6-Hydroxy-2,4-Dimethoxylbenzaldehyde was prepared from anhydrous phloroglucinol via Vilsmeier-Hack reaction and dimethylation. The product reacted with 4-methoxyphenylpropan-1-one in the precence of dry HCl gas to give the flavylium salt. The benzofuran product was obtained after oxidation of the salt by H2O2. Three synthetic routes were designed based on this important intermediate.In the first route, the former structures of the target compouds were obtained by Adol and Knoevenagel reactions. The last step is synthesis of the cyclopentane ring which contains two cis adjacent aryl and phenyl substituents via Nazarov cyclization. After a great deal of attempts, we gave up this reactions. Nevertheless, we accumu -lated some experience and synthesized several new compounds.Some preliminary research has been conducted in the second route. An efficient method to synthesize of 1-(2-(4-methoxyphenyl)benzofuran-3-yl)ethanone has been discovered and the Claisen rearrangement of the intermediate has been studied. It is hopefull to complete the last three steps.In the third route, The [2+2] photocyclization is still under research. In the future research, the main task is to find a suitable solvent and light condition.更多还原