Enantioselective Total Synthesis of Breviones Utilizing a Bio-Inspired Skeletal Editing Strategy

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Biosynthesis

Background:

• Spiro diterpene pyrones are complex natural products with potential biological activities.
• Understanding their biosynthesis can inspire novel synthetic strategies.
• Previous synthetic routes have limitations in accessing these intricate structures.

Purpose of the Study:

• To develop an enantioselective total synthesis of meroditerpenoids breviones B, C, and N.
• To showcase bio-inspired skeletal editing transformations for constructing spiro diterpene pyrones.
• To establish a versatile synthetic methodology for related natural products.

Main Methods:

• Utilized a Dowd-Beckwith ring expansion for seven-membered A-ring construction.
• Employed an annulative skeletal rearrangement to couple terpene and α-pyrone motifs.
• Developed a novel dihydropyran-to-dihydrofuran ring contraction strategy.
• Implemented a SnCl₄-mediated intramolecular hydroalkylation of alkenyl β-keto esters.

Main Results:

• Successfully synthesized breviones B, C, and N with high enantioselectivity.
• Demonstrated the efficacy of bio-inspired skeletal editing transformations.
• Established a new method for concurrent assembly of fused B/C ring systems with three stereocenters.
• Showcased the applicability of the dihydropyran-to-dihydrofuran ring contraction to diverse fragments.

Conclusions:

• The developed synthetic strategy provides efficient access to breviones and related meroditerpenoids.
• Bio-inspired skeletal editing transformations are powerful tools for complex natural product synthesis.
• The novel ring contraction and hydroalkylation methods offer broad utility in organic synthesis.