Structure Revision of Lyciumamides A-C and Their Hypoglycemic Activities

Area of Science:

• Natural Product Chemistry
• Organic Chemistry
• Pharmacology

Background:

• Lyciumamides A-C were initially reported as novel phenolamide dimers from Lycium barbarum.
• Previous research suggested alternative structures, identifying them as known compounds but lacked sufficient data.
• Discrepancies in structural assignments and configuration determination necessitated further investigation.

Purpose of the Study:

• To revise and confirm the structures of lyciumamides A-C using advanced spectroscopic methods.
• To determine the relative and absolute configurations of the identified compounds.
• To evaluate the biological activities of the revised compounds, particularly compound 3b.

Main Methods:

• 1D and 2D Nuclear Magnetic Resonance (NMR) experiments for structural elucidation.
• Carbon-13 (13C) NMR calculations to support structural assignments.
• Electronic Circular Dichroism (ECD) spectroscopy for absolute configuration determination.

Main Results:

• The structures of lyciumamides A-C were revised to cannabisin F (1), grossamide (2b), and grossamide K (3b).
• Relative and absolute configurations of grossamide (2b) and grossamide K (3b) were successfully assigned.
• Compound 3b demonstrated the ability to promote preadipocyte differentiation.
• Compound 3b exhibited agonistic activity towards peroxisome proliferator-activated receptor (PPAR) in adipocytes.

Conclusions:

• The structures of lyciumamides A-C have been definitively revised, clarifying their identity as known compounds.
• The stereochemistry of grossamide (2b) and grossamide K (3b) has been established.
• Compound 3b possesses significant biological activity, highlighting its potential therapeutic relevance in adipocyte function and metabolic regulation.