Synthesis of Archaeal Macrocyclic Etherial Lipids and Their Properties

古菌大环醚脂的合成及其性质

• 批准号: 07680623
• 负责人: EGUCHI Tadashi
• 金额: $ 1.34万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680623/
• 关键词: Synthesis; Archaea; Membrane Lipid; Macrocyclic Lipid

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

古细菌（archaebacteria）包括产甲烷菌、极端嗜盐菌、极端嗜热菌和嗜热嗜酸菌，它们在相当特殊的条件下生长，并具有结构独特的膜脂以适应极端环境。脂质由通过醚键与甘油连接的疏水性类异戊二烯链组成，这与真细菌和真核细胞膜脂质的酯键形成鲜明对比。古细菌醚脂质最显着的特征是在大环（36 或 72 元）环结构中发现的。人们对这些不寻常的脂质与基于脂质双层结构的理化性质的联系感兴趣。我们对这些脂质的兴趣集中在大环分子结构的生化意义上。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纯形式的古细菌脂质。已经实现了古菌36元大环二醚脂质的全合成。该合成基于官能化类异戊二烯链的立体选择性制备、类异戊二烯链与甘油衍生物之间形成醚键，以及使用低价钛（称为 McMurry 偶联）的最终分子内二羰基偶联。这种合成方法成功地提供了第一个化学确定的古菌大环膜脂的实用途径，该途径由于缺乏合成途径而无法获得。还研究了古细菌 72 元四醚脂质的去甲基化类似物的合成。高稀释条件下的 McMurry 偶联反应成功生成了 72 元大环产物。我们的实验室目前正在将该方法扩展到天然古菌 72 元大环四醚脂质的合成中。此外，合成脂质的特性目前也在研究中。较少的

项目成果

T.Eguchi,他3名: "Total Synthesis of Archaeal 36-Membered Macrocyclic Diether Lipid" J.Org.Chem.(印刷中).

T.Eguchi 和其他 3 人：“古细菌 36 元大环二醚脂质的全合成”J.Org.Chem。

T.Eguchi,H.Kano,K.Kakinuma: "Synthetic studies of archaeal macrocyclic tetraether lipids-a versatile approach to desmethylated analogues of the 72-membered macrocycylic diphytanyldiglycerol." J.Chem.Soc.,Chem.Commun.,. (印刷中).

T.Eguchi、H.Kano、K.Kakinuma：“古细菌大环四醚脂质的合成研究 - 72 元大环二植烷基二甘油去甲基化类似物的通用方法。”J.Chem.Soc.，Chem.Commun.，（目前正在印刷中）。

T.Eguchi 他2名: "Synthetic Study on Archaeal Macrocyclic Tetraether Lipids-A Versatile Approach to Desmethylated Aralogs of 72-Membered Dibiphytanyldiglycerol" Chem.Commun.365-366 (1996)

T. Eguchi 和另外 2 人：“古细菌大环四醚脂质的合成研究 - 72 元二二植烷基二甘油去甲基化 Aralog 的通用方法” Chem.Commun.365-366 (1996)

T.Eguchi 他3名: "Total Synthesis of Archaeal 36-Membered Macrocyclic Diether Lipid" J.Org.Chem.(印刷中)

T.Eguchi 和其他 3 人：“古菌 36 元大环二醚脂质的全合成”J.Org.Chem。

T.Eguchi, H.Kano, K.Kakinuma: "Synthetic Study on Archaeal Macrocyclic Tetraether Lipids-A Versatile Approarch to Desmethylated Analogs of 72-Membered Dibiphytanyldiglycerol" Chem.Commun. (2). 365-366 (1996)

T.Eguchi、H.Kano、K.Kakinuma：“古菌大环四醚脂质的合成研究 - 72 元二二植烷基二甘油去甲基化类似物的多功能方法”Chem.Commun。