Total synthesis and assignment of configuration of the thiazoline-based cyclopeptide cyclodidemnamide isolated from the sea squirt Didemnum molle

Abstract

A total synthesis of the proposed structure 1 for the oxazoline/thiazoline-based cyclopeptide cyclodidemnamide, isolated from the sea squirt Didemnum molle, is described. The synthesis features a novel double cyclodehydration, sequential formation of chiral thiazoline and oxazoline rings in a preformed cyclopeptide intermediate, as a key stratagem. The NMR spectroscopic data for synthetic 1 and natural cyclodidemnamide did not correlate. The configuration of the natural product was re-assigned as 15, the C-15-(R)-Val epimer, which was confirmed by total synthesis.