Total Syntheses of Aromatic Abietane Diterpenoids Utilizing Advances in the Pummerer Rearrangement

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Natural products like triptobenzene T and vitexifolin C possess complex structures with significant biological relevance.
• Establishing the absolute stereochemistry of these molecules is crucial for understanding their activity and for future drug development.

Purpose of the Study:

• To achieve the first total syntheses of triptobenzene T, vitexifolin C, 4-epi-triptobenzene L, triptobenzene L, and nepetaefolin F.
• To confirm or establish the absolute stereochemistry of these natural products.
• To showcase novel synthetic methodologies applicable to complex molecule synthesis.

Main Methods:

• Enantioselective synthesis utilizing a common intermediate approach.
• Application of three new or underutilized Pummerer reaction pathways.
• Proline sulfonamide-catalyzed Yamada-Otani reaction for constructing the cyclohexane A ring core and a quaternary stereocenter.

Main Results:

• Successful total synthesis of five target natural products.
• Confirmation and/or establishment of the absolute stereochemistry for all synthesized compounds.
• Demonstration of the critical role of A ring unsaturation in controlling stereoselectivity during C4 alkylation.

Conclusions:

• The developed synthetic strategy provides access to complex natural products and their stereoisomers.
• The study validates novel Pummerer reaction pathways and a proline sulfonamide-catalyzed Yamada-Otani reaction for complex synthesis.
• This work advances the field of natural product synthesis and stereochemical determination.