本文選題：石松科生物堿 + 串聯反應��； 參考：《蘭州大學》2017年博士論文

【摘要】：石松屬包含上千個不同的種,且在全世界范圍均有分布。石松作為藥用植物,在世界上有著悠久的歷史。從石松中分離得到的生物堿更是結構多樣、生物活性顯著,由于石松科生物堿的這些特性,它一直吸引著諸多合成化學家和藥物化學家的研究興趣。本學位論文著重于圍繞著lycodoline型和Fawcettimine型石松科生物堿的生源啟發(fā)的全合成。以lycojaponicumin D的仿生合成為驅動,以lycodoline為基礎,設計、發(fā)展了串聯的碎裂化/Mannich環(huán)化反應,實現了由lycodoline到lycojaponicumin D的生源啟發(fā)的仿生轉化,建立了6/6/6/6骨架結構和5/7/6/6四環(huán)體系的重排聯系�；趯ΨQ化切斷的策略,發(fā)展了新穎的Pd介入的串聯氧化脫氫/hetero-Michael加成反應,實現了雙環(huán)[3.3.1]體系橋頭C?H的官能團化,為發(fā)展基于Saugesa-Ito氧化的串聯反應提供了新的機遇。以lycodoline為契機的發(fā)散式合成,總共實現了9個石松科天然產物堿、4類天然石松科生物堿的合成,其中l(wèi)ycojaponicumin D和6個lycodoline型石松科生物堿(lycoposerramine G,miyoshianine A,obscurumine A,serratezomine C,huperzine O,and 12-epilycodoline)屬于首次全合成報道。本論文主要包含以下三個部分:第一章:系統(tǒng)地介紹了石松科生物堿的分離、活性、分類及部分合成工作。第二章:以lycojaponicumin D生源啟發(fā)的仿生合成為動力,設計發(fā)展了“串聯的碎裂化/Mannich環(huán)化反應”,實現了lycaponicumin D的全合成報道。在基于對稱性切斷策略,設計發(fā)展了新穎的“串聯氧化脫氫/hetero-Michael加成反應”,為張力橋環(huán)體系中橋頭C?H鍵的雜原子官能團化提供了新方法。在此基礎上結合“串聯還原胺化/橋頭胺解反應”,簡潔高效地實現了lycodoline的克級化學合成。第三章:采用兩種不同的策略嘗試12-epilycodoline的全合成研究,并最終通過羥基消除和烯烴水合的方式,完成了12-epilycodoline的首次合成。同時基于lycodoline的發(fā)散式合成,完成了4個lycodoline型石松科生物堿以及4個類天然產物的合成。第四章:針對fawcettimine類石松科生物堿的合成,首先嘗試了aza-semipinacol重排反應的仿生合成策略。隨后設計了以Pauson?Khand插羰環(huán)化為關鍵反應的匯聚式合成路線,并對關鍵的Pauson?Khand反應做了初步的化學探討。
[Abstract]:Pinus contains thousands of different species and is distributed all over the world. Pine, as a medicinal plant, has a long history in the world. The alkaloids isolated from Pinus lanceolata have various structures and remarkable biological activities. Because of these properties of alkaloids, they have attracted the research interest of many synthetic chemists and pharmaceutical chemists. This dissertation focuses on the total synthesis of biogenic alkaloids of lycodoline type and Fawcettimine type of Pinaceae. Based on the bionic synthesis of lycojaponicumin D and lycodoline, a series of fragmentation / Mannich cyclization reaction was designed and developed. The bionic transformation inspired by lycodoline to lycojaponicumin D was realized, and the skeleton structure of 6 / 6 / 6 / 6 and the rearrangement of 5 / 7 / 6 / 6 four-ring system were established. Based on the strategy of symmetry cutting, a novel series oxidative dehydrogenation / hetero-Michael addition reaction involving PD was developed, and the functionalization of Con H at the bridgehead of bicyclic [3.3.1] system was realized, which provided a new opportunity for the development of series reaction based on Saugesa-Ito oxidation. A total of 9 natural alkaloids of Pinaceae were synthesized by using lycodoline as the opportunity of divergent synthesis. Lycojaponicumin D and 6 lycodoline type alkaloids of Pinaceae, lycojaponicumin D and 6 lycodoline type alkaloids of Pinaceae Gobsoserramine, are reported for the first time in the total synthesis of Chuperzine and 12-epilycodolineine, among which lycojaponicumin D and 6 lycodoline type alkaloids of Pinaceae are reported for the first time in the total synthesis report of Chuperzine and 12-epilycodoline.Aobscuranine Aobsratezomine Chuperzine and 12-epilycodoline are reported for the first time. This paper mainly includes the following three parts: chapter 1: the separation, activity, classification and partial synthesis of alkaloids of Pinaceae are introduced systematically. Chapter 2: based on the bionic synthesis inspired by lycojaponicumin D, the series fragmentation / Mannich cyclization reaction is designed and developed, and the full synthesis report of lycaponicumin D is realized. Based on the symmetry cut-off strategy, a novel "series oxidative dehydrogenation / hetero-Michael addition reaction" was designed and developed, which provides a new method for the functionalization of the C ~ (+) H bond at the bridgehead in the tension bridge ring system. Combined with series reduction amination / bridgehead amination reaction, lycodoline was synthesized succinctly and efficiently. Chapter 3: two different strategies were used to study the total synthesis of 12-epilycodoline. Finally, the first synthesis of 12-epilycodoline was completed by hydroxyl elimination and olefins hydration. At the same time, based on the divergent synthesis of lycodoline, four lycodoline alkaloids and four natural products were synthesized. Chapter 4: in view of the synthesis of fawcettimine alkaloids, the bionic synthesis strategy of aza-semipinacol rearrangement reaction was first tried. Then a convergent synthesis route with Pauson?Khand intercalated carbonyl ring as the key reaction was designed and the key Pauson?Khand reaction was preliminarily studied.
【學位授予單位】：蘭州大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：O629.3

【相似文獻】

相關期刊論文 前1條

1 ;石松科生物堿(±)-Alopecuridine和(±)-Sieboldine A的全合成[J];有機化學;2011年08期

相關博士學位論文 前4條

1 趙憲鶴;生源啟發(fā)的Lycodoline型和Fawcettimine型石松科生物堿合成研究[D];蘭州大學;2017年

2 王芳昕;石松科生物堿Palhinine A和Palhinine D全合成研究[D];蘭州大學;2017年

3 張國彪;石松科生物堿Palhinine A合成研究[D];蘭州大學;2013年

4 張曉明;石松科生物堿Alopecuridine，Sieboldine A和Lycojapodine A的全合成[D];蘭州大學;2013年

，

本文編號：1805815