手性二酮化合物的拆分以及倍半萜Aquatolide的全合成

发布时间：2018-03-15 10:09

  本文选题：拆分　切入点：二酮　出处：《中国科学技术大学》2017年博士论文　论文类型：学位论文

【摘要】：本文主要分为两章,分别研究了:对2,3:6,7-二苯并二环[3.3.1]-2,6-庚烯-4,8-二酮的拆分和对倍半萜Aquatolide的全合成。第一章是高效地拆分2,3:6,7-二苯并二环[3.3.1]-2,6-庚烯-4,8-二酮化合物并对其进行衍生化的研究。本章通过手性1,1'-联-2-萘酚直接对上述二酮进行拆分,而且成功得到了拆分中间体的单晶结构,通过X射线单晶衍射,观测到1,1'-联-2-萘酚羟基氢与酮羰基之间的氢键相互作用,并且确定了产物的绝对构型。这种拆分方法高效且实用,可以放大到克级的规模,通过一次拆分就能以大于85%的总产率和大于99%的ee值得到上述手性二酮,而且手性1,1'-联-2-萘酚还可以以大于95%的产率回收,其ee值也没有发生任何变化。我们还对上述二酮进行衍生化研究,合成了几种手性醇和手性胺类化合物。第二章是对倍半萜Aquatolide的全合成。从环戊二烯基钠出发,通过25步反应完成了对Aquatolide的全合成。首先采用一种较为温和的方法构建重氮化合物,然后通过沃尔夫重排反应,以一种比较高效的方法构建了具有较大张力的四元环结构。对于八元环的合成,我们设计了两条合成路线:第一条路线中,尝试通过分子内的醛对炔烃进行加成来构建八元环结构,但我们没有得到产物;第二条路线是基于Z式三取代的碘代烯烃,通过Nozaki-Hiyama-Kishi反应构建最后一个八元环骨架,然后经过斯文氧化合成了倍半萜Aquatolide。
[Abstract]:This paper is divided into two chapters. The resolution of [3.3.1] -2o 6-heptene-4-octene-8-dione and the total synthesis of p-sesquiterpene Aquatolide were studied respectively. The first chapter is about the efficient resolution and derivation of 2 ~ (3: 3): 6 ~ (7) -dibenzobicyclo [3.3.1] -26-heptene-4N ~ (8-dione). The above mentioned diketones are directly resolved by chiral 1H 1C-BIS-2-naphthol, The single crystal structure of the intermediate was successfully obtained. The hydrogen bond interaction between hydroxyl hydrogen and ketone carbonyl group was observed by X-ray single crystal diffraction. And the absolute configuration of the product is determined. The method is efficient and practical, and can be enlarged to the scale of gram class. By one resolution, the chiral diketone can be obtained at a total yield of more than 85% and ee greater than 99%. Moreover, the chiral 1H 1C Bis 2 naphthol can be recovered in a yield greater than 95%, and its ee value has not changed in any way. We have also studied the derivatization of the above mentioned diketones. Several chiral alcohols and chiral amines have been synthesized. Chapter 2 is the total synthesis of p-sesquiterpene Aquatolide. The total synthesis of Aquatolide was completed in 25 steps. First, a mild method was used to construct diazo compounds, and then through the Wolff rearrangement reaction, A quaternary ring structure with high tension is constructed by a more efficient method. For the synthesis of octa-ring, we have designed two synthetic routes: in the first route, An attempt was made to construct an octa-ring structure by the addition of intramolecular aldehydes to alkynes, but we did not get the product. The second route was based on the Z-type tri-substituted iodinated alkenes, and the last octa-ring skeleton was constructed by Nozaki-Hiyama-Kishi reaction. Then the sesquiterpene Aquatolide was synthesized by Sven oxidation.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O622
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本文编号：1615563