Divergent Synthesis of Six Recent Berkeleylactones

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Berkeleylactones are a class of recently isolated natural products with potential biological activity.
• The total synthesis of these complex molecules presents significant chemical challenges.

Purpose of the Study:

• To develop a divergent synthetic strategy for the first-time synthesis of berkeleylactones E, J, K, M, N, and O.
• To establish a stereoselective method for constructing the γ,δ-dihydroxy-α,β-unsaturated ester moiety.
• To achieve a high-yielding formal synthesis of the antibiotic A26771B.

Main Methods:

• A divergent synthetic strategy was employed, starting from a common intermediate.
• Stereoselective formation of the γ,δ-dihydroxy-α,β-unsaturated ester was a key step.
• A general protection group strategy was developed and applied.

Main Results:

• Successful first-time synthesis of berkeleylactones E, J, K, M, N, and O.
• Development of a robust and efficient synthetic route.
• Established a short, high-yielding formal synthesis of antibiotic A26771B.

Conclusions:

• The developed divergent strategy is effective for synthesizing a series of berkeleylactones.
• The synthetic methodology provides access to valuable natural products and antibiotic precursors.
• This work expands the synthetic accessibility of complex lactone natural products.