Structural Investigation of Aaptourinamine by a Novel Module-Assembly-Based Calculation

Area of Science:

• Natural Product Chemistry
• Computational Chemistry
• Organic Synthesis

Background:

• Elucidating complex natural product structures is challenging due to limitations in conventional analytical methods, particularly with high C/H ratios or proton-deficient compounds.
• Two-dimensional nuclear magnetic resonance (2D NMR) correlations are often insufficient for complete structural determination of such molecules.

Purpose of the Study:

• To develop and validate a novel computational method for the structural elucidation of natural products with complex and challenging structures.
• To apply this new method to identify the structure of aaptourinamine, a compound isolated from the marine sponge *Aaptos suberitoides*.

Main Methods:

• Development of the 'Dooerafa' module-assembly calculation method.
• Incorporation of a grafting method using limited 2D NMR correlations.
• Application of a ring-contraction strategy combining mechanic force field and quantum chemical theory.
• Utilizing self-assemble calculations in Python and Density Functional Theory-Gauge-Independent Atomic Orbital (DFT-GIAO) calculations.

Main Results:

• The Dooerafa method was successfully validated using the known alkaloid spiroreticulatine, whose structure was confirmed by X-ray diffraction.
• The method enabled the structural elucidation of aaptourinamine, revealing a novel imidazo[4,5,1-ij]pyrrolo[3,2-f]quinolin-7(8H)-one scaffold.
• A biosynthetic relationship between aaptourinamine and the known bioactive alkaloid aaptamine was proposed.

Conclusions:

• The novel Dooerafa computational method is effective for determining complex natural product structures, overcoming limitations of traditional techniques.
• The elucidation of aaptourinamine provides a new chemical scaffold and insights into the biosynthesis of marine sponge alkaloids.