Ligand Type Guided Keto-Arylation Enables Modular Total Synthesis of Polycyclic CBS Xanthones.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Polycyclic xanthones are potent antibiotics with complex structures.
• Previous synthetic routes were limited, hindering access to these valuable compounds.

Purpose of the Study:

• To achieve the first total synthesis of the polycyclic xanthone antibiotics CBS72, CBS87, and CBS100.
• To develop and validate a novel modular synthetic strategy for complex natural products.

Main Methods:

• A modular synthetic strategy was employed, featuring intermolecular aromatic keto-arylation.
• An asymmetric Davis hydroxylation was utilized with catalytic base on a sensitive substrate.
• Late-stage aminolysis completed the polycyclic framework, avoiding extensive protecting group manipulations.

Main Results:

• The first total synthesis of CBS72, CBS87, and CBS100 was successfully accomplished.
• The developed strategy proved efficient and high-yielding, confirming the full architecture of these xanthones.
• A ligand-type approach was demonstrated as effective for complex target synthesis.

Conclusions:

• The developed modular strategy provides concise and high-yielding access to potent polycyclic xanthone antibiotics.
• This work validates the utility of ligand-type approaches in complex molecule synthesis.
• The synthesis confirms the complete structure of this important class of natural products.