Studies towards the Synthesis of Leiodolide A

Two dienes comprising the complete heavy-atom framework of the macrocyclic core of the marine macrolide leiodolide A were prepared by esterification of an appropriate carboxylic acid and two alcohol building blocks. The latter were obtained in a stereoselective fashion from (R)-citronellal via a Crimmins-type aldol reaction, oxidative double bond cleavage, and efficient oxazole formation as the key transformations. The possible ring-closing metathesis (RCM) based macrocyclization of the dienes was investigated under different conditions. None of the cyclized product was obtained in any of these experiments, thus indicating that RCM between C6 and C7 may not be a viable strategy for the total synthesis of leiodolide A.