Synthesis of Archaeal Macrocyclic Etherial Lipids and Their Properties

古细菌包括产甲烷菌、极端嗜盐菌、极端嗜热菌和嗜热嗜酸菌，它们在非常特殊的条件下生长，并具有结构独特的膜脂以适应极端环境。脂质由疏水性类异戊二烯链与甘油醚键连接组成，这与真细菌和真核生物膜脂质的酯键形成鲜明对比。古细菌醚脂最显著的特征是大环（36或72元）环结构。这些不寻常的脂质已经与基于脂质双层结构的物理化学性质有关。我们对这些脂质的兴趣集中在大环分子结构的生物化学意义上。前提是开发大环脂质的合成方法，因为很难从天然来源获得大量的纯形式的古细菌脂质。 ...更多信息 合成了古细菌36元大环二醚脂。该合成是基于立体选择性制备功能化的类异戊二烯链，醚键之间的类异戊二烯链与甘油衍生物的形成，并在最终的分子内二羰基偶联使用低价钛称为麦克默里耦合。这种合成方法成功地提供了化学定义的古细菌大环膜脂，这是不可用的，因为缺乏合成途径的第一个实用的路线。还研究了古细菌72元四醚脂质的去甲基化类似物的合成。在高稀释条件下的McMurry偶联反应成功地得到了72元大环产物。目前，我们实验室正在将这种方法扩展到天然古菌72元大环四醚脂质的合成。此外，合成脂质的性质目前也在研究中。少

Archaea (archaebacteria) including methanogens, extreme halophiles, extreme thermophiles and thermoacidophiles grow under rather extraordinary conditions and have structurally unique membrane lipids to adapt the extreme environments. The lipids are consisted of hydrophobic isoprenoid chains linked to glycerol with the ether bonds, which are well contrast to the ester linkage of the eubacterial and eukaryotic membrane lipids. The most striking feature of the archaebacterial ether lipid is found in the macrocyclic (36-or 72-membered) ring structures. These unusual lipids have been interested in connection with the physicochemical properties based on the lipid bilayr structure. Our interest in these lipids focuses on the biochemical significance of the macrocyclic molecular structures. Prerequisite is to develop synthetic methods of the macrocyclic lipids, because it is difficult to obtain significant amount of the archaebacterial lipids in pure form from natural sources.Total synthesis o … More f archaeal 36-membered macrocyclic diether lipid has been achieved. The synthesis is based upon stereoselective preparation of functionalized isoprenoid chains, ether-linkage formation between the isoprenoid chains with a glycerol derivative, and on the ultimate intramolecular dicarbonyl coupling using low-valent titanium known as McMurry coupling. This synthetic method has successfully provided the first practical route to chemically defined archaeal macrocyclic membrane lipids, which were not available because of the lack of synthetic access. Also investigated is the synthesis of desmethylated analogs of archaebacterial 72-membered tetraether lipids. The McMurry coupling reaction under high dilution conditions yielded successfully the 72-membered macrocyclic product. Extension of this methodology to the synthesis of natural archaeal 72-membered macrocyclic tetraether lipids is currently underway in our laboratory. Furthermore, the properties of the synthesized lipid are also currently under study. Less