Annulative Methods Enable a Total Synthesis of the Complex Meroterpene Berkeleyone A

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Complex meroterpenes are fungal natural products with significant medicinal interest.
• Synthetic pathways for meroterpenes derived from 3,5-dimethylorsellinic acid (DMOA) and farnesyl pyrophosphate are currently unreported.
• Berkeleyone A is a potential gateway compound to various fungal meroterpenes.

Purpose of the Study:

• To achieve the first total synthesis of berkeleyone A.
• To develop a novel annulation reaction for the synthesis of hydroxylated 1,3-cyclohexadiones.

Main Methods:

• A 13-step synthetic pathway was designed and executed for berkeleyone A.
• A novel annulation reaction was developed and optimized for synthesizing hydroxylated 1,3-cyclohexadiones.

Main Results:

• The first total synthesis of berkeleyone A was successfully accomplished in 13 steps.
• A novel, single-step annulation reaction for hydroxylated 1,3-cyclohexadiones was developed.
• This work provides a crucial synthetic route to berkeleyone A and related meroterpenes.

Conclusions:

• The reported synthesis of berkeleyone A provides access to a valuable class of fungal meroterpenes.
• The novel annulation reaction expands the synthetic toolkit for constructing complex cyclic compounds.
• This research opens avenues for further exploration of fungal meroterpenes and their medicinal applications.