A Metathesis-Based Approach toward the Convergent Synthesis of Populusene A

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Populusene A, a diterpene from *Populus euphratica*, exhibits anti-inflammatory properties.
• It targets pro-inflammatory proteins and transcription factors regulating inflammatory cytokines.

Purpose of the Study:

• To develop an effective synthesis of cycloheptenone 5, a crucial intermediate for populusene A.
• To optimize a metathesis cyclization strategy for constructing the core structure.

Main Methods:

• Synthesis of diene precursors for metathesis cyclization.
• Modification of the metathesis precursor by replacing a terminal olefin with a phenyl-equipped disubstituted alkene.
• Protection of the β-keto phosphonate as an enol carbonate.

Main Results:

• Initial metathesis attempts were largely unsuccessful.
• Key structural modifications led to a practical and high-yielding cyclization.
• The optimized approach minimized homodimerization and favored the desired cyclization.

Conclusions:

• The modified metathesis strategy provides an efficient route to cycloheptenone 5.
• This synthetic approach can be applied to other challenging metathesis cyclizations.
• The synthesis advances the preparation of populusene A and related anti-inflammatory compounds.