Scalable Total Synthesis of Acremolactone B

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Acremolactone B is a pyridine-containing azaphilone-type polyketide.
• The complex structure of Acremolactone B presents a significant synthetic challenge.

Purpose of the Study:

• To achieve the first total synthesis of Acremolactone B.
• To develop an efficient and scalable synthetic route for Acremolactone B.

Main Methods:

• A key aza-6π electrocyclization-aromatization strategy was employed to construct the tetra-substituted pyridine ring.
• A bicyclic intermediate was synthesized via [2+2] photocycloaddition and Baeyer-Villiger oxidation.
• The tetracyclic core was assembled through an electrocyclization-aromatization cascade, followed by side chain introduction.

Main Results:

• The total synthesis of Acremolactone B was successfully accomplished on a gram scale.
• The developed synthetic strategy proved effective for constructing the complex polyketide.

Conclusions:

• The first total synthesis of Acremolactone B was reported.
• The study highlights the utility of the aza-6π electrocyclization-aromatization strategy in natural product synthesis.