Synthesis of 6-epi-Hypersampsone R by a Desymmetrization Strategy

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of natural products with diverse biological activities.
• The bicyclo[3.3.1]nonane-2-8-dione core found in hypersampsone R is structurally rare and challenging to synthesize.

Purpose of the Study:

• To develop an efficient and scalable synthetic route to 6-epi-hypersampsone R.
• To establish a general strategy for the synthesis of structurally related PPAPs.

Main Methods:

• A 10-step synthesis was designed, starting with the creation of an achiral bicyclic bis-enone.
• Key steps included bridgehead functionalization, desymmetrization, and a one-pot conjugate addition/acylation.

Main Results:

• Successfully synthesized 6-epi-hypersampsone R in 10 steps.
• Achieved high-yielding and scalable synthesis of the key bicyclic intermediate.
• Demonstrated a novel one-pot strategy for constructing the final carbon-carbon bonds.

Conclusions:

• The reported synthetic approach provides an effective route to 6-epi-hypersampsone R.
• The general strategy of core synthesis, desymmetrization, and functionalization can be applied to other PPAP compounds.
• This work expands the synthetic accessibility of complex PPAPs.