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

【摘要】：石松屬包含上千個(gè)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(jié)構(gòu)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(xué)家和藥物化學(xué)家的研究興趣。本學(xué)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(qū)動(dòng),以lycodoline為基礎(chǔ),設(shè)計(jì)、發(fā)展了串聯(lián)的碎裂化/Mannich環(huán)化反應(yīng),實(shí)現(xiàn)了由lycodoline到lycojaponicumin D的生源啟發(fā)的仿生轉(zhuǎn)化,建立了6/6/6/6骨架結(jié)構(gòu)和5/7/6/6四環(huán)體系的重排聯(lián)系。基于對(duì)稱化切斷的策略,發(fā)展了新穎的Pd介入的串聯(lián)氧化脫氫/hetero-Michael加成反應(yīng),實(shí)現(xiàn)了雙環(huán)[3.3.1]體系橋頭C?H的官能團(tuán)化,為發(fā)展基于Saugesa-Ito氧化的串聯(lián)反應(yīng)提供了新的機(jī)遇。以lycodoline為契機(jī)的發(fā)散式合成,總共實(shí)現(xiàn)了9個(gè)石松科天然產(chǎn)物堿、4類天然石松科生物堿的合成,其中l(wèi)ycojaponicumin D和6個(gè)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(bào)道。本論文主要包含以下三個(gè)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(dòng)力,設(shè)計(jì)發(fā)展了“串聯(lián)的碎裂化/Mannich環(huán)化反應(yīng)”,實(shí)現(xiàn)了lycaponicumin D的全合成報(bào)道。在基于對(duì)稱性切斷策略,設(shè)計(jì)發(fā)展了新穎的“串聯(lián)氧化脫氫/hetero-Michael加成反應(yīng)”,為張力橋環(huán)體系中橋頭C?H鍵的雜原子官能團(tuán)化提供了新方法。在此基礎(chǔ)上結(jié)合“串聯(lián)還原胺化/橋頭胺解反應(yīng)”,簡(jiǎn)潔高效地實(shí)現(xiàn)了lycodoline的克級(jí)化學(xué)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(shí)基于lycodoline的發(fā)散式合成,完成了4個(gè)lycodoline型石松科生物堿以及4個(gè)類天然產(chǎn)物的合成。第四章:針對(duì)fawcettimine類石松科生物堿的合成,首先嘗試了aza-semipinacol重排反應(yīng)的仿生合成策略。隨后設(shè)計(jì)了以Pauson?Khand插羰環(huán)化為關(guān)鍵反應(yīng)的匯聚式合成路線,并對(duì)關(guān)鍵的Pauson?Khand反應(yīng)做了初步的化學(xué)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(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：O629.3

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本文編號(hào)：1805815