Asymmetric Total Synthesis of (+)-Shearilicine

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Indoloditerpenoids are a class of complex natural products with potential biological activity.
• The total synthesis of complex molecules is crucial for structure elucidation and analog development.

Purpose of the Study:

• To report the first asymmetric total synthesis of indoloditerpenoid shearilicine.
• To achieve the first total syntheses of related compounds, including epi-shearilicine and a key vinyl ether intermediate.

Main Methods:

• Asymmetric total synthesis strategy.
• Late-stage Achmatowicz rearrangement for pyran derivative formation.
• Final cyclization step to construct the indoloditerpenoid core.
• Ketal formation for intermediate synthesis.

Main Results:

• Successful asymmetric total synthesis of shearilicine (1).
• First total syntheses of epi-shearilicine (27) and vinyl ether intermediate (26) achieved.
• Demonstration of a robust synthetic route amenable to analog preparation.

Conclusions:

• The developed synthetic route provides access to shearilicine and its analogs.
• This work expands the synthetic toolbox for complex indoloditerpenoids.
• The synthesized compounds can serve as standards for natural product research.