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.