Facile methods to determine double-bond positions in long-chain olefins and absolute configurations of α-hydroxy acids

Even with modern spectroscopic techniques and advanced knowledge in organic chemistry, structural determinations of some natural products require tedious and challenging processes. We developed new methods to facilitate the structural determinations of long-chain olefins (Kwon, Y.; Lee, S.; Oh, D.-C.; Kim, S. Angew. Chem. Int. Ed. 2011, 50, 8275) and α-hydroxy acid-bearing depsipeptides (Moon, K.; Lim, C.; Kim, S.; Oh, D.-C. Chem. Comm. in preparation). The positions of double bonds in unsaturated long-chain compounds can be easily determined by chemical derivatization using a cross-metathesis reaction and chromatography-mass spectrometry. The produced olefins have distinct physicochemical properties suitable for LC/MS or GC/MS analysis that depend on the cross-metathesis partner used. In addition, the absolute configurations of α-hydroxy acids can be established by a modified reaction with Marfey's reagent. This reaction derivatizes the α-hydroxy groups of α-hydroxy acids along with the amine groups of amino acids. This generates their diastereomeric derivatives, enabling simultaneous determination of the absolute configurations of α-hydroxy acids and α-amino acids in a depsipeptide by LC/MS analysis. We also show successful applications of these new methods to real natural products. Our new procedures are practically useful because of their simple application to natural products at a submilligram scale.