Total Synthesis of Clerodin

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• Clerodin is the earliest isolated clerodane diterpenoid.
• Developing efficient and asymmetric synthetic routes is crucial for natural product chemistry.

Purpose of the Study:

• To achieve the first asymmetric total synthesis of clerodin.
• To establish novel synthetic strategies for clerodane diterpenoids.

Main Methods:

• Tail-to-head cyclization of an epoxide ene-yne.
• Titanium(III) catalyzed epoxide ring-opening/ene-yne cyclization.
• Metallaphotoredox-enabled deoxygenative coupling for furan fragment assembly.
• Samarium(II) iodide-mediated elimination for dihydrofuran motif construction.

Main Results:

• Successfully synthesized the C19 oxidized trans-decalin core.
• Efficiently assembled the furan fragment.
• Established the 2,3-dihydrofuran motif.
• Achieved the first asymmetric total synthesis of clerodin.

Conclusions:

• The developed modular synthetic strategies enable efficient access to clerodin.
• This synthesis provides a robust platform for further exploration of clerodane diterpenoids.