Structural Elucidation of Micro-Scale Natural Products through Analytical and Synthetic Approaches

Area of Science:

• Chemistry
• Natural Products Chemistry
• Analytical Chemistry

Background:

• Natural products possess remarkable structural variety and are crucial in chemical ecology, biological interactions, and drug discovery.
• Many natural products are scarce, posing significant analytical challenges for structural elucidation.

Purpose of the Study:

• To review landmark studies and recent advancements in the structural analysis of natural products available in microgram to sub-milligram quantities.
• To focus on Nuclear Magnetic Resonance (NMR)-based elucidation and complementary techniques.

Main Methods:

• High-field NMR instrumentation, cryogenic probes, and advanced pulse sequences.
• Comparison with synthetic standards, Density Functional Theory (DFT)-assisted structure validation.
• Crystalline sponge method and Microcrystal Electron Diffraction (MicroED).

Main Results:

• Integrated analytical and synthetic strategies enable reliable structure determination from minute quantities of natural products.
• Demonstrated application in analyzing natural toxins, biosynthetic intermediates, and microbial signaling molecules.

Conclusions:

• Advanced methodologies are essential for determining the structures of limited natural product samples.
• These techniques are foundational for natural product discovery, biosynthesis, and understanding biological activity and chemical ecology.