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
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.