Synthesis of palmyrolide A and its cis-isomer and mechanistic insight into trans–cis isomerisation of the enamide macrocycle

Abstract

Concise and protecting-group free synthesis of ent-palmyrolide A and (-)-cis-palmyrolide A were achieved starting from commercially available (S)-citronellal. The key fragment of palmyrolide A, "(5S,7S)-7-hydroxy-5,8,8-trimethylnonanamide", which makes up the most challenging part of the target molecule, was prepared in just three steps. A plausible mechanism for the trans-cis isomerization of the double bond in the macrocycle has been investigated.