Total Synthesis and Structural Revision of Lucentamycin A

Abstract

Lucentamycin A is a marine-derived peptide natural product harboring a unique 4-ethylidene-3-methylproline (Emp) subunit. The proposed structure of lucentamycin A and the core Emp residue have recently been called into question through synthesis. Here, we report the first total synthesis of lucentamycin A, which confirms that the ethylidene substituent in Emp bears an <i>E</i> geometry, in contrast to the originally assigned <i>Z</i> configuration. Synthesis of the desired (<i>E</i>)-Emp subunit required the implementation of a novel strategy starting from Garner’s aldehyde