Combining JBCA and Marfey's methodology to determine the absolute configuration of threonines: the case of gunungamide A, a new cyclic depsipeptide containing chloropyrrole from the sponge Discodermia sp.

Abstract

A combination of configurational analysis based on coupling constants (JBCA) and Marfey's aminoacid derivatization allowed us to distinguish between the different possible diastereoisomers of threonines in cyclopeptides, when potentially some of the amino acids could be racemized/epimerized during the acid hydrolysis process. The strategy was applied to a new cyclic depsipeptide having an unusual chloropyrrol ring, gunungamide A (2), isolated from a marine sponge belonging to the genus Discodermia. Further validation of this approach was demonstrated with the peptide stellatolide (1), where epimerization of a threonine residue during hydrolysis in the Marfey's analysis resulted in a mistaken configuration. This approach can be extended to elucidate the absolute stereochemistry of peptides bearing amino acids with two or more contiguous chiral centers.