Total synthesis of (+)-crotogoudin

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Stereoselective Synthesis

Background:

• Diterpenoids, including 3,4-seco-atisanes, are complex natural products with potential biological activities.
• The total synthesis of such molecules presents significant challenges in constructing intricate polycyclic frameworks.

Purpose of the Study:

• To report the first total synthesis of the natural product (+)-crotogoudin.
• To establish a synthetic route to the bicyclo[2.2.2]octane core.
• To determine the absolute configuration of (+)-crotogoudin.

Main Methods:

• Asymmetric synthesis utilizing baker's yeast for desymmetrization of a meso-diketone.
• SmI2-induced radical cascade reactions for cyclopropane-opening, annulation, and elimination.
• Stereochemical analysis and assignment of absolute configuration.

Main Results:

• Successful construction of the tetracyclic structure of (+)-crotogoudin.
• Development of an efficient asymmetric route to the bicyclo[2.2.2]octane core.
• Revision of the reported optical rotation and assignment of the absolute configuration as ent-atisane (5R,10R).

Conclusions:

• The first total synthesis of (+)-crotogoudin has been accomplished.
• The synthetic strategy provides access to the challenging 3,4-seco-atisane diterpenoid scaffold.
• The absolute configuration of the natural product has been definitively assigned.