TOTAL SYNTHESIS OF ARCHAEAL 72-MEMBERED MACROCYCLIC TETRAETHER LIPIDS

Total synthesis of archaeal 72-membered macrocyclic tetraether lipids 3a and 3b is reported. The synthesis was principally composed of prepa ration of the functionalized half-sized diether compounds 11 and 15 fi rst followed by appropriate dimerization through Julia coupling and fi nal macrocyclization of the crucial dialdehydes 23 and 31 by McMurry c oupling. This strategy appeared to be advantageous for the stereoselec tive synthesis of both natural 72-membered tetraether lipids 3a and 3b using common synthetic intermediates. In addition, this approach was so designed that its synthetic flexibility would allow construction of unnatural structural variants for physicochemical studies. Also descr ibed are the results of differential scanning calorimetric analysis of the synthesized lipids 3a and 3b. Both 3a and 3b showed almost the sa me phase behavior with the broad endothermic phase transition at -53 d egrees C. The enthalpy of the phase transition, Delta H, was estimated to be 1.8 and 1.9 kcal/mol for 3a and 3b, respectively. The physicoch emical as well as polymorphismic properties of 3a and 3b turned out to be indistinguishable despite of their regioisomeric structures. The p hysical structure of the phases in terms of the chemical structure is also discussed.