Bio-inspired total synthesis of daphnepapytone A

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Methodology Development

Background:

• Guaiane sesquiterpenes are a class of natural products with complex structures.
• Daphnepapytone A is a unique sesquiterpene featuring a bridged, highly substituted cyclobutane ring.
• Developing efficient synthetic routes to complex natural products is crucial for chemical biology and drug discovery.

Purpose of the Study:

• To achieve the first total synthesis of daphnepapytone A.
• To develop a bio-inspired synthetic strategy for constructing the guaiane skeleton and its unique bridged cyclobutane.
• To synthesize other related guaiane natural products and potentially revise their structures.

Main Methods:

• Eschenmoser-Tanabe fragmentation of (R)-carvone epoxide.
• Allenylation followed by a regioselective allenic Pauson-Khand reaction to form the guaiane skeleton.
• Biomimetic [2 + 2]-photocycloaddition for constructing the bridged cyclobutane.
• Late-stage C-H oxidation and stereoselective reduction.

Main Results:

• Successful total synthesis of daphnepapytone A (1).
• Efficient construction of the guaiane skeleton and the bridged cyclobutane motif.
• Total synthesis of oleodaphnone (3), diarthroncha C, and daphnenicillata W.
• Structural revision of one of the synthesized guaiane natural products.

Conclusions:

• The developed synthetic strategy is effective for accessing complex guaiane sesquiterpenes.
• The study highlights the utility of bio-inspired approaches and key reactions like the allenic Pauson-Khand and biomimetic photocycloaddition.
• This work expands the known synthetic routes to valuable natural products and contributes to structural elucidation in the field.