Synthesis of Modified Fusicoccane Diterpenoids via Diverging MHAT Reactivity

Area of Science:

• Natural Product Synthesis
• Chemical Biology
• Protein-Protein Interactions

Background:

• Cotylenin and fusicoccin are diterpene glycosides known to modulate 14-3-3 protein-client interactions.
• 14-3-3 proteins are crucial regulators of diverse cellular processes, and their interactions are vital for cell signaling.
• Understanding the structural basis of these interactions is key to developing chemical tools for biological studies.

Purpose of the Study:

• To report the divergent synthesis of brassicicene (BR-I) and talarmalnoid B (Tal-B) aglycons.
• To provide access to key structural motifs of biologically active diterpene glycosides.
• To facilitate further studies on the mechanism by which these compounds modulate 14-3-3 protein interactions.

Main Methods:

• Modification of Studer's Mukaiyama hydration variant for diterpene synthesis.
• Total synthesis strategies for complex natural product aglycons.
• Characterization of synthetic intermediates and final products using spectroscopic methods.

Main Results:

• Successful divergent synthesis of brassicicene (BR-I) and talarmalnoid B (Tal-B) aglycons was achieved.
• The synthetic route employed a modified Mukaiyama hydration strategy.
• The synthesized aglycons serve as valuable precursors for generating the corresponding glycosides.

Conclusions:

• The developed synthetic methodology provides efficient access to key diterpene aglycons.
• These synthetic aglycons are important for further investigation into the modulation of 14-3-3 protein interactions by cotylenin and fusicoccin analogs.
• This work contributes to the chemical biology toolbox for studying protein-protein interaction modulation.