Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision**

  • Mira Holzheimer
  • , Jaap S. Sinninghe Damsté
  • , Stefan Schouten
  • , Remco W.A. Havenith
  • , Ana V. Cunha
  • , Adriaan J. Minnaard

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.

Original languageEnglish
Pages (from-to)17504-17513
Number of pages10
JournalAngewandte Chemie - International Edition
Volume60
Issue number32
DOIs
StatePublished - Aug 2 2021
Externally publishedYes

Funding

The authors would like to thank Dr. J. Buter and E. Jonkheim (University of Groningen) for their contribution to the isolation of crenarchaeol. P. van der Meulen and Dr. J. Kemmink (University of Groningen) are acknowledged for their assistance in NMR measurements. This work was sponsored by NWO Exact and Natural Sciences for the use of supercomputer facilities and RWAH and AV thank S. Dolas (SURF, NL) for allowing to perform experiments on the experimental AMD platform kleurplaat, maintained and operated by SURF Open Innovation Lab. This project received funding to JSSD from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 694569, MICROLIPIDS).

Keywords

  • archaea
  • crenarchaeol
  • structure revision
  • tetraether lipid
  • total synthesis

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