Total synthesis of cyclohexadepsipeptides exumolides A and B

Exumolides A and B are two cyclodepsipeptides that was previously isolated from marine fungus. Both peptides were synthesized using a combination of solid- and solution-phase method. The linear precursor was synthesized through solid-phase method on 2-chlorotrityl resin with standard Fmoc strategy. The hydroxy acid, (S)-2-hydroxy-4-methylpentanoic acid (Hmp), was prepared from its precursor l -leucine, and attached on the resin with a double-coupling protocol. The depside bond formation that was carried out at the end of the coupling process, was beneficial, particularly, in the blockage of the diketopiperazine formation during Fmoc deprotection. The cyclic product was obtained through HATU-based cyclisation. Exumolides A and B were successfully synthesized with overall yields of 4.12% and 6.39%, respectively.