Synthesis of over 30-Membered Giant Ring Compounds : Synthetic Study of Archaeal 36- and 72-Membered Macrocyclic Membrane Lipids

Abstract

Total synthesis of archaeal 36- and 72-membered macrocyclic membrane lipids and their model compounds using several methodologies are described. The first was the diacetylene coupling known as Glaser reaction for construction of macrocyclic phosphodiester model compounds. For the synthesis of archaeal macrocyclic membrane lipids, we made use of two methodologies for the macrocyclization. The ultimate intramolecular dicarbonyl coupling using low-valent titanium successfully provided the 36- and 72-membered macrocyclic compounds with 50-70% yield. In addition, a new and efficient approach to the macrocyclic lipids using olefin metathesis allowed us to successfully prepare both 36-and 72-membered compounds from the same precursor by using the proper conditions.