Studies on Functional Role of Archaeal Etherial Lipids

古生菌包括产甲烷菌、极端嗜盐菌、极端嗜热菌和嗜热酸菌，它们在相当特殊的条件下生长，并具有结构独特的膜脂来适应极端环境。这些脂类是由疏水的异戊二烯链通过醚键连接到甘油上，这与真细菌和真核生物膜脂的酯键形成了很好的对比。古细菌乙醚类化合物最显著的特征是在大环(36元或72元)环结构中被发现。这些不寻常的脂类一直对基于脂类双层结构的物理化学性质感兴趣。我们对这些脂类的兴趣集中在大环分子结构的生物化学意义上。开发大环脂类化合物的合成方法是前提，因为从天然来源中很难获得大量纯净的古生菌类脂。我们是第一个合成古生菌…的人更多的36元和72元大环脂使用麦克默里偶联。此外，最近还实现了一种利用烯烃歧化反应制备大环脂类化合物的新方法。在格拉布斯试剂RuCl2(=CHPh)(PCy3)2存在下，α，ω-二烯的闭环歧化反应在高稀释条件下以79%的产率进行，得到36元脂类。通过改变反应条件，从相同的底物中主要生成了非环二烯歧化(ADM)产物。非环产物随后在高稀释条件下进行RCM反应，得到46%的72元脂类。因此，只需改变歧化反应的顺序和条件，就可以从同一原料中随意地得到36元和72元的脂类。从流动性、热稳定性和渗透性等方面考察了36元大环磷脂与相应的非环磷脂的物理化学特征。热分析和单层研究表明，36元大环磷脂由于其在烷基链区的运动自由度较小，可以聚集成比相应的无环磷脂更紧密的堆积结构，此外，我们还发现大环结构有助于热稳定膜的形成。这些趋势似乎与嗜热古菌詹纳斯基甲烷球菌对高温的耐受性有关。较少

Archaea 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 archaeal 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 bilayer 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 archaeal lipids in pure form from natural sources.We were the first in synthesizing the archaeal … More 36- and 72-membered macrocyclic lipids using McMurry coupling. In addition, a new and efficient approach to the macrocyclic lipids using olefin metathesis has been accomplished recently. In the presence of a Grubbs' ruthenium-alkylidene complex, RuCl_2(=CHPh)(PCy_3)_2, a ring closing metathesis (RCM) of α, ω-diene efficiently proceeded in 79% yield under high dilution conditions to give 36-membered lipid. By changing the reaction conditions, an acyclic diene metathesis (ADM) product was predominantly formed from the same substrate. The acyclic product was subsequently subjected to the RCM reaction under high dilution conditions to provide 72-membered lipid in 46%. Thus, both 36- and 72- membered lipids can be obtained at will from the same starting material only by changing the order and conditions of the metathesis reaction.The physicochemical features of the 36-membered macrocyclic phospholipid were investigated in comparison with the corresponding acyclic counterpart in terms of fluidity, thermostability and permeability of the liposomes. Thermal analyses and monolayer studies indicated that the 36-membered macrocyclic phospholipid can aggregate to more tightly packed structures than the corresponding acyclic counterpart due to its less motional freedom at the alkyl chain region.Furthermore, we found that the macrocyclic structure contributed to the formation of thermally stable membrane. These tendencies appear to be related to the tolerance of thermophilic archaea Methanococcus jannaschii against high temperature. Less