Total synthesis of crotophorbolone

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Diterpenoid Chemistry

Background:

• Crotophorbolone is a natural diterpenoid featuring a complex trans,trans-5/7/6 framework.
• It possesses six contiguous stereogenic centers and is structurally related to bioactive tigliane diterpenoids like phorbol and prostratin.

Purpose of the Study:

• To achieve the first total synthesis of crotophorbolone.
• To establish a synthetic route for accessing this complex natural product and its analogs.

Main Methods:

• Employed a convergent synthetic strategy.
• Utilized (-)-carvone and (+)-dimethyl-2,3-O-isopropylidene-l-tartrate as starting materials.
• Key steps included early installation of fused rings, seven-membered ring cyclization via alkenylation, functional group-sensitive ring-closing metathesis, and selective hydroxylations.

Main Results:

• Successfully completed an eighteen-step total synthesis of crotophorbolone.
• Demonstrated the feasibility of constructing the challenging trans,trans-5/7/6 framework with six stereocenters.

Conclusions:

• The total synthesis of crotophorbolone has been accomplished.
• This provides a valuable platform for further investigation into the biological activities of crotophorbolone and related tigliane diterpenoids.