Magnusson Carlos D, Gudmundsdottir Anna V, Hansen Kai-Anders, Haraldsson Gudmundur G
Science Institute, University of Iceland, Dunhaga 3, 107 Reykjavik, Iceland.
Mar Drugs. 2015 Jan 7;13(1):173-201. doi: 10.3390/md13010173.
This report describes the synthesis of reversed structured 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGEs) possessing a pure saturated even number fatty acid (C6:0-C16:0) at the sn-2 position along with a pure EPA or DHA located at the terminal sn-3 position of the glycerol backbone of chimyl, batyl and selachyl alcohols. These adducts were synthesized by a highly efficient two-step chemoenzymatic process involving an immobilized Candida antarctica lipase to introduce pure EPA and DHA activated as oxime esters exclusively to the sn-3 terminal position of enantiopure chimyl, batyl and selachyl alcohols in excellent yields. The saturated fatty acids were subsequently incorporated to the remaining sn-2 position of the resulting 3-monoacylglyceryl ethers (3-MAGEs) using EDAC coupling agent in the presence of DMAP in very high to excellent yields (85%-98%). No losses of enantiomeric composition were observed during these processes. The multiple utilities of the resulting focused library of reversed structured DAGEs are discussed including how such compounds may possibly be utilized within the pharmaceutical area.
本报告描述了具有反向结构的1-O-烷基-2,3-二酰基-sn-甘油(DAGEs)的合成,这些化合物在sn-2位具有纯的饱和偶数脂肪酸(C6:0-C16:0),同时在鲨肝醇、巴豆醇和鲨油醇甘油主链的末端sn-3位含有纯的二十碳五烯酸(EPA)或二十二碳六烯酸(DHA)。这些加合物通过高效的两步化学酶法合成,该方法涉及固定化的南极假丝酵母脂肪酶,将作为肟酯活化的纯EPA和DHA仅以优异的产率引入对映体纯的鲨肝醇、巴豆醇和鲨油醇的sn-3末端位置。随后,在4-(N,N-二甲基氨基)吡啶(DMAP)存在下,使用1-乙基-3-(3-二甲基氨基丙基)碳二亚胺(EDAC)偶联剂,以非常高至优异的产率(85%-98%)将饱和脂肪酸引入所得的3-单酰基甘油醚(3-MAGEs)的剩余sn-2位。在这些过程中未观察到对映体组成的损失。讨论了所得的反向结构DAGEs聚焦文库的多种用途,包括这些化合物在制药领域可能的应用方式。