20 古細菌大環状脂質の合成及びその膜機能(口頭発表の部)

抄録

Archaea (archaebacteria) grow under the extreme environments such as hot springs, highly saline lakes, and deep-sea volcanoes. These microorganisms possess unique membrane lipids composed of isoprenoid chains which bind to glycerol by ether linkage. More interestingly, some archaea have macrocyclic ether lipids as large as 36- or 72-membered ring sizes. Our interest focuses on the biochemical significance of the macrocyclic molecular structures. We were the first in synthesizing the archaeal 36- and 72-membered macrocyclic lipids (2, 3a and 3b) 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 17 efficiently proceeded in 79% yield under high dilution conditions to give 36-membered 18. By changing the reaction conditions, an acyclic diene metathesis (ADM) product 19 was predominantly formed from the same substrate 17. The acyclic product 19 was subsequently subjected to the RCM reaction under high dilution conditions to provide 72-membered compound 20 in 46%. Thus, both 18 and 20 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 phospholipids 21 were investigated in comparison with the corresponding acyclic counterpart 22 in terms of fluidity, thermostability and permeability of the liposomes. Thermal analyses and monolayer studies indicated that 21 can aggregate to more tightly packed structures than 22 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.