Asymmetric synthetic study of macrolactin analogues

We designed two aromatic analogues and of macrolactin A with expectation of enhancing biological activity and metabolical stability. As a result of retrosynthetic analysis of these compounds , two synthetic strategies have been examined. The first strategy includes the enantioselective addition of nonadienyl anion, derived from , to aldehyde as a key step. The second one includes epimerization of ynone to (E,E)-conjugated dienone and subsequent diastereoselective hydride-reduction of . Although the former route furnished no desired target, the latter one was revealed to work well for the synthesis of . Unfortunately, the aimed (2Z,4E)-analogue could not be synthesized due to an epimerization of the (2Z)-olefin into the (2E)-olefin. However, these methods could be applied to the total asymmetric synthesis of the (2E,4E)-analogue . Overall, control of all of the four stereocenters was achieved by means of asymmetric and diastereoselective reactions without using any chiral natural sources.