Enantioselective Total Synthesis of the Archaeal Lipid Parallel GDGT‐0 (Isocaldarchaeol)**

Abstract

Archaeal glycerol dibiphytanyl glycerol tetraethers (GDGT) are some of the most unusual membrane lipids identified in nature.T hese amphiphiles are the major constituents of the membranes of numerous Archaea, some of which are extremophilic organisms.D ue to their unique structures, there has been significant interest in studying both the biophysical properties and the biosynthesis of these molecules. However,these studies have thus far been hampered by limited access to chemically pure samples.Herein, we report aconcise and stereoselective synthesis of the archaealt etraether lipid parallel GDGT-0 and the synthesis and self-assembly of derivatives bearing different polar groups.

Archaeal Glycerolipids Are Recognized by C-Type Lectin Receptor Mincle

“…Scheme a shows the syntheses of archaeal lipids 1 and 2 . Some synthetic routes to the archaeal lipids and their related lipids, including chemical synthesis − and semisynthesis, , have been reported. One of the critical steps toward their syntheses is a β-selective glycosylation between sugars and archaeol 3 .…”

Structure-Function Relationships in Pure Archaeal Bipolar Tetraether Lipids

“…In earlier work led by the Burns group, an efficient synthetic route to the core structure of parallel GDGT-0 (iso-caldarchaeol) was described. 19 In the same work, the synthesis of P2 and P1Glc were reported. In this work, along with P2 and P1Glc, the synthesis of two additional GDGT lipids -PG2 and PG1Glc was achieved (Figure 2, Supplementary Schemes S1-7).…”

“…Differential scanning calorimetry (DSC) studies on bulk GDGT lipid mixtures from extracts typically revealed that the lipids exist in fluid phases at all temperatures and do not exhibit any endothermic phase transitions. 19 However, it may be challenging to detect transitions like lamellar to hexagonal which are typically characterized by low enthalpy changes. 44 Moreover, each DSC measurement requires a significant amount of material that is not always practical to recover.…”

“…Only a handful of examples exist where polar GDGT lipids have been synthesized via total synthetic or semisynthetic approaches. 9,[17][18][19] To date, no GDGT lipids can be purchased from commercial vendors in pure form. Therefore, most biophysical studies until now have been performed on crude lipid extracts [20][21][22][23][24] or model bipolar lipids.…”