Isolation and computer-based structural determination of madangolide b

Madangolide (1) is a 17-membered cyclic enamide isolated from the marine
cyanobacterium Lyngbya bouillonii. Since its discovery in 1999, the
relative and absolute configurations of 1 have remained unknown. Here, we
report the isolation, structural determination, and biological activity of
a new analog of madangolide (1), madangolide B (2), from a marine Moorena
sp. cyanobacterium. The planar structure of 2 was established using
conventional two-dimensional NMR spectroscopy. The absolute configuration
was clarified by comparing the experimental and theoretical data,
including the chemical shifts, homonuclear and heteronuclear coupling
constants, and ECD spectra. Based on the similarity of the NMR data, we
proposed an absolute configuration of madangolide (1) and verified it
through degradation and derivatization reactions. This study demonstrates
the effectiveness of modern computational chemistry in revealing the
stereochemistry of complex natural products with conformational
flexibility.