Isolation and Computer-Based Structural Determination of Madangolide B.

Area of Science:

• Marine natural product chemistry
• Organic chemistry
• Computational chemistry

Background:

• Madangolide (1) is a cyclic enamide from marine cyanobacteria.
• Its relative and absolute configurations remained unknown since its 1999 discovery.
• Marine cyanobacteria are a source of complex bioactive molecules.

Purpose of the Study:

• To isolate and determine the structure of madangolide B (2), a new analog.
• To clarify the absolute configuration of madangolide B (2) and madangolide (1).
• To showcase the utility of computational chemistry in natural product stereochemistry.

Main Methods:

• Isolation of madangolide B from a *Moorena* sp. cyanobacterium.
• Structure elucidation using 2D NMR spectroscopy.
• Absolute configuration determination via comparison of experimental and theoretical NMR chemical shifts, coupling constants, and ECD spectra.
• Verification of madangolide (1) configuration through degradation and derivatization.

Main Results:

• Madangolide B (2) was isolated and its planar structure determined.
• The absolute configuration of madangolide B (2) was successfully assigned.
• The absolute configuration of madangolide (1) was proposed and verified.
• Computational chemistry proved effective for complex, conformationally flexible natural products.

Conclusions:

• The absolute configurations of madangolide and madangolide B were determined.
• Modern computational chemistry is a powerful tool for natural product stereochemistry.
• This study expands the understanding of madangolide natural products.