Synthesis of Archaeal Macrocyclic Etherial Lipids and Their Properties

点击翻译按钮获取中文摘要

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