Enantioselective Total Synthesis of the Archaeal Lipid Parallel GDGT‐0 (Isocaldarchaeol). Issue 32 (11th June 2021)

• Record Type: Journal Article
• Authors: Falk, Isaac D.; Gál, Bálint; Bhattacharya, Ahanjit; Wei, Jeremy H.; Welander, Paula V.; Boxer, Steven G.; Burns, Noah Z.
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 32(2021)
• Page Start: 17491
• Page End: 17496
• Publication Date: 2021-06-11
• Subjects: archaeal lipids -- asymmetric hydrogenation -- macrolactonization -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202104051
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Archaeal glycerol dibiphytanyl glycerol tetraethers (GDGT) are some of the most unusual membrane lipids identified in nature. These amphiphiles are the major constituents of the membranes of numerous Archaea, some of which are extremophilic organisms. Due 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 a concise and stereoselective synthesis of the archaeal tetraether lipid parallel GDGT‐0 and the synthesis and self‐assembly of derivatives bearing different polar groups. Abstract : A rapid, enantioselective synthesis of parallel GDGT‐0 is reported using a global asymmetric hydrogenation to set all 16 methyl stereocenters. An unprecedented macrolactonization‐hydrosilylation sequence then constructs the 72‐membered macrocyclic lipid. Desymmetrization enabled the synthesis of a GDGT‐0 with different headgroups. Phase transition and self‐assembly studies gave evidence that the lipids form fluid giant unilamellar vesicles.