Total synthesis of (+)-iresin

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Stereoselective Synthesis

Background:

• (+)-Iresin is an historically significant ent-Drimane sesquiterpene lactone.
• The synthesis of complex natural products presents significant challenges in stereocontrol and efficiency.

Purpose of the Study:

• To achieve the first asymmetric total synthesis of (+)-iresin.
• To develop novel synthetic methodologies applicable to sesquiterpene lactones.

Main Methods:

• The synthesis commenced from aldehyde 3, proceeding through cyclic orthoester 6 in a 5-step sequence.
• Key transformations included a tandem trifluoroperacetic acid (TFPAA)-mediated Baeyer-Villiger oxidation-olefin epoxidation-epoxy ester cyclization.
• Regioselective Burgess dehydration and regioselective Fétizon oxidative lactonization were also employed.

Main Results:

• Successful completion of the first asymmetric total synthesis of (+)-iresin.
• Demonstration of the utility of the developed synthetic sequence and key transformations.
• Confirmation of the structure and stereochemistry of the synthesized (+)-iresin.

Conclusions:

• The developed 5-step synthetic route provides an efficient and stereoselective access to (+)-iresin.
• The employed tandem reactions and regioselective transformations represent valuable additions to the synthetic chemist's toolkit.
• This synthesis paves the way for further exploration of ent-Drimane sesquiterpene lactones and their biological activities.