AN OLEFIN METATHESIS APPROACH TO 36-MEMBERED AND 72-MEMBERED ARCHAEALMACROCYCLIC MEMBRANE-LIPIDS

An olefin metathesis approach, which has been successfully applied to an efficient synthesis of archaeal 36- and 72-membered macrocyclic mem brane lipids (1, 2a, and 2b), is reported. In the presence of a Grubbs ' ruthenium-alkylidene complex, RuCl2(=CHPh)(PCy3)(2) (3), a ring-clos ing metathesis (RCM) reaction of alpha,omega-diene 5 efficiently proce eded in 79% yield under high dilution conditions to give 36-membered 6 . By changing the reaction conditions, a acyclic diene metathesis (ADM ) product 7 was predominantly formed from the same substrate 5. The ac yclic product 7 was subsequently subjected to the RCM reaction under h igh dilution conditions to provide 72-membered compound 8 in 45% yield . Final catalytic hydrogenation of 6 and 8 afforded the 36-membered li pid I and a mixture of the 72-membered lipid 2a and 2b, respectively. The present synthetic method appears to be of significant advantage fo r the synthesis of such giant ring structures of the 36- and 72-member ed lipids, because both of the macrocylic lipids can be obtained in a short step at will from the same starting material only by changing th e order and conditions of the metathesis reaction.