Total synthesis and antimalarial activity of mortiamides A-D

Mortiamides A–D (1–4) are head-to-tail cyclic heptapeptides that were identified from a novel Mortierella sp. isolate obtained from marine sediments from Northern Canada. Herein we report the first total synthesis of mortiamides A–D (1–4) on a solid support by concomitant cyclization/cleavage without any oligomerization side reactions, and overall yields up to 48%. We also report on the antiplasmodial activity of mortiamides A–D (1–4). We show that three out of the four tested mortiamides (A, B and D) have moderate antiplasmodial activity, while mortiamide D (4) exhibits low micromolar activity.