Total Synthesis of the Membrane Spanning Tetraether Lipid brGDGT Ia and Elucidation of Its Stereochemical Configuration

Glycerol dialkyl glycerol tetraethers (GDGTs) are a group of membrane spanning lipids produced by both Archaea and Bacteria. Branched GDGTs (brGDGTs) are a class of these tetraether lipids known to be produced by certain bacteria and are commonly found in terrestrial environments. Due to their environmental ubiquity, high preservation potential, and role in membrane adaptation, brGDGTs form the basis of many widely employed paleoenvironmental proxies. The tetramethylated brGDGT Ia is the most commonly reported branched tetraether in cultured Acidobacteria and is a key component of brGDGT-based temperature indices. Herein, we report the first total synthesis of brGDGT Ia, thereby elucidating the relative configuration of the methyl branches as syn. We further demonstrate that VCD spectroscopy is a suitable tool to determine the absolute configuration of these cryptochiral compounds, a method waiting to be applied to the natural lipid, but currently hampered by its limited availability.