Total synthesis of gambierol: subunit coupling and completion

Area of Science:

• Organic Synthesis
• Total Synthesis
• Natural Product Chemistry

Background:

• Previous work established the synthesis of key gambierol ring precursors.
• Gambierol is a complex marine natural product with potential biological activity.
• Efficient synthetic routes are crucial for accessing complex molecules like gambierol.

Purpose of the Study:

• To describe the coupling of advanced gambierol precursors.
• To complete the total synthesis of (-)-gambierol.
• To develop an efficient synthetic strategy minimizing post-coupling modifications.

Main Methods:

• Coupling of advanced subunits via ester formation.
• Application of enol ether ring-closing metathesis (RCM).
• Utilization of mixed thioketal formation and reduction for subunit linkage.

Main Results:

• Successfully coupled the advanced gambierol precursors.
• Generated 7.5 mg of (-)-gambierol.
• Achieved a 1.5% overall yield in a 44-step longest linear sequence.

Conclusions:

• The developed strategy efficiently assembled gambierol from advanced precursors.
• Minimizing post-coupling transformations is key to streamlining complex syntheses.
• This work provides a viable route to (-)-gambierol and demonstrates strategic coupling methods.