Complete Stereochemical Assignment of Campechic Acids A and B

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Natural Product Synthesis

Background:

• Campechic acids A and B are polyketide natural products with demonstrated anti-invasive properties.
• These compounds are isolated from Streptomyces sp. CHI93, presenting a challenge for large-scale production and structural elucidation.
• Understanding the precise stereochemistry of these complex molecules is crucial for their biological activity and potential therapeutic applications.

Purpose of the Study:

• To achieve a stereoselective synthesis of the C-16-C-30 fragment of campechic acids A and B.
• To assign and potentially reassign the absolute configurations of stereogenic centers within this fragment.
• To compare synthetic intermediates with degradation products using advanced spectroscopic techniques.

Main Methods:

• Employed a biosynthesis-inspired epoxide-opening cascade for the stereoselective construction of the target fragment.
• Utilized Nuclear Magnetic Resonance (NMR) spectroscopy for detailed structural analysis and comparison.
• Synthesized and analyzed authentic degradation products for direct spectroscopic comparison.

Main Results:

• Successfully synthesized the C-16-C-30 fragment of campechic acids A and B with high stereocontrol.
• Configurational assignment was achieved for stereocenters C-21, C-24, C-25, and C-28.
• Reassignment of the stereochemistry at the C-18 center was determined through comparative NMR analysis.

Conclusions:

• The stereoselective synthesis provides a reliable route to a key fragment of campechic acids.
• The confirmed and reassigned stereochemistry refines the structural understanding of these anti-invasive antibiotics.
• This work facilitates further synthetic efforts and the exploration of campechic acids as potential therapeutic agents.