Synthesis of Optically Pure Diglycerol Tetraether Model Lipids with Non‐Natural Branching Pattern

Abstract

AbstractThree new, chain‐modified, optically pure diglycerol tetraether lipids with one membrane‐spanning chain have been synthesised. These lipids contain a different number and constitution of the methyl branches connected to the hydrophobic chains as compared with natural archaeal or other previously synthesised lipids. The correct chirality of the branched alkyl chain was introduced starting from commercially available (S)‐citronellyl bromide. For chain elongation the Cu‐catalysed Grignard coupling reaction was used. Suitable blocked glycerol ethers were condensed to the tetraether moieties by Grubbs metathesis. The insertion of two or four optically pure methyl branches at the 10‐ and/or 23‐positions of the alkyl chains are sufficient to mimic the main properties of natural tetraether lipids. In this context, it has been shown that these lipids can form closed lipid vesicles.