天然产物Myrtucommulone K,N和O的仿生合成研究

发布时间：2018-03-06 10:39

本文选题：Myrtucommulone　切入点：K　出处：《兰州大学》2017年硕士论文　论文类型：学位论文

【摘要】：本论文以选择性还原消除多羰基化合物和杂狄尔斯-阿尔德(Hetero-Diels Alder Reaction)反应为关键反应对天然产物Myrtucommulone K,N和O进行仿生合成研究,并总结了以氧杂二烯为双烯体进行不对称杂狄尔斯-阿尔德反应的研究进展,分为以下二个部分:第一章天然产物Myrtucommulone K,N和O的仿生合成研究Myrtucommulone K,N和O是2016年从香桃木叶子中分离出来的混源萜类化合物,MTT检测对人体肝癌细胞和乳腺癌细胞有一定的抑制活性。在分离文献中推测它们的生源合成途径是天然产物flavesone经过选择性还原消除生成isobutylidenesyncarpic acid,再与β-caryophyllene的环内双键发生oxa-Diels-Alder反应生成两个差向异构体Myrtucommulone K和N,而与β-caryophyllene的环外双键发生oxa-Diels-Alder反应则生成具有特殊的螺环结构的Myrtucommulone O。这些天然产物的生物活性和生源合成途径引起了我们的关注,文献调研发现β-caryophyllene的环外双键活性较低,在2016年7月以前也没有关于β-caryophyllene的环外双键参与Diels-Alder反应的报道。为了完成Myrtucommulone K,N和O的仿生合成,我们首先参照文献的合成方法制备了isobutylidenesyncarpic acid,用该化合物与β-caryophyllene进行oxa-Diels-Alder反应,经条件优化合成了Myrtucommulone K,N和O,其收率分别为25%,8%和42%。从反应结果来看在该反应中,β-caryophyllene的环外双键比环内双键反应活性高。在flavesone经过还原消除生成isobutylidenesyncarpic acid的仿生合成中,采用多种还原试剂对flavesone中的羰基进行选择性还原,然后在酸性条件下脱水生成isobutylidenesyncarpic acid,最终发现DABAL-H可以很好的实现选择性还原异丁酰基上的羰基成羟基,并在HCl的作用下脱水生成isobutylidenesyncarpic acid。结合flavesone的仿生选择性还原消除和oxa-Diels-Alder反应,使得仅用4步反应就完成了天然产物Myrtucommulone K,N和O的首次全合成。第二章氧杂二烯作为双烯体的HDA反应研究二氢吡喃及其衍生物是一种常见的六元杂环化合物,广泛存在于天然产物的结构中,在合成领域也有重要应用。在关于它的逆电子效应的HDA反应合成中,氧杂二烯作为双烯体由于其活性低一直未受到足够重视,近年来逐步发展了一些新的催化手段,可以在温和条件下以较高的产率和立体选择性得到期望的二氢吡喃结构,扩大了该方法的应用范围。本章概述了20多年来氧杂二烯作为双烯体发生不对称HDA反应的方法及其最新研究进展。
[Abstract]:In this paper, selective reduction elimination of polycarbonyl compounds and Hetero-Diels Alder reaction were used as the key reactions to study the bionic synthesis of natural products Myrtucommulone Kno N and O. The research progress of asymmetric heterodiene reaction with oxadiene as diene was also summarized. Chapter 1 Biomimetic Synthesis of Natural products Myrtucommulone Kno N and O; Myrtucommulone Kno N and O were isolated from the leaves of Peachwood in 2016. It is suggested in the literature that the natural product flavesone is selectively reduced to form isobutylidenesyncarpic acid.Then oxa-Diels-Alder reacts with 尾 -caryophyllene to produce two differential isomers Myrtucommulone K and N, respectively. The oxa-Diels-Alder reaction with 尾 -caryophyllene produced Myrtucommulone O with special snail ring structure. The biological activity and biosynthesis pathway of these natural products have attracted our attention. It was found that the activity of 尾 -caryophyllene was low, and there was no report that 尾 -caryophyllene had participated in the Diels-Alder reaction before July 2016. In order to complete the bionic synthesis of Myrtucommulone Kno N and O, there were no reports on the involvement of 尾 -caryophyllene in the Diels-Alder reaction before July 2016. Firstly, isobutylidenesyncarpic acidwas prepared by referring to the synthetic method in literature. The compound reacted with 尾 -caryophyllene for oxa-Diels-Alder reaction. Myrtucommulone Kon N and O were synthesized in 25% and 42% yields, respectively. According to the reaction results, the activity of 尾 -caryophyllene was higher than that of in-ring double bond reaction. In the bionic synthesis of isobutylidenesyncarpic acid, flavesone was reduced and eliminated. The carbonyl groups in flavesone were selectively reduced by various reductive reagents, and then dehydrated under acidic conditions to form isobutylidenesyncarpic acid. finally, it was found that DABAL-H could selectively reduce carbonyl groups to hydroxyl groups on isobutyryl groups. Isobutylidenesyncarpic acid. combined with the bionic selective reduction elimination of flavesone and oxa-Diels-Alder reaction, The first total synthesis of natural products Myrtucommulone Kno N and O was completed by using only four steps. Chapter 2 the HDA reaction of oxadiene as a diene; dihydropyran and its derivatives are a common hexagonal heterocyclic compound. Oxadiene has been widely used in the structure of natural products and has important applications in the field of synthesis. In the HDA reaction synthesis of its inverse electron effect, oxadiene as a diene has not been paid enough attention to because of its low activity. In recent years, some new catalytic methods have been developed to obtain the desired dihydropyran structure under mild conditions with high yield and stereoselectivity. In this chapter, the methods of asymmetric HDA reaction of oxadiene as dienes and their latest research progress are summarized.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O629

【相似文献】