Total synthesis of isokidamycin

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• The pluramycin family comprises complex natural products with potential biological activities.
• Bis-C-aryl glycosides are a challenging subclass of natural products to synthesize.
• Isokidamycin is a significant target within the pluramycin family.

Purpose of the Study:

• To achieve the first total synthesis of the natural product isokidamycin.
• To develop novel synthetic strategies for constructing bis-C-aryl glycoside linkages.
• To explore the utility of silicon-tethered intramolecular Diels-Alder reactions in complex molecule synthesis.

Main Methods:

• Total synthesis of isokidamycin.
• Application of a silicon tether for regiocontrol in an intramolecular Diels-Alder reaction.
• Utilized a substituted naphthyne and a glycosyl furan as key reaction partners.
• Performed a subsequent O→C-glycoside rearrangement.

Main Results:

• Successful completion of the first total synthesis of isokidamycin.
• Demonstrated the efficacy of a silicon tether in controlling regioselectivity.
• Established a viable route for constructing the bis-C-aryl glycoside core structure.
• The O→C-glycoside rearrangement was successfully employed.

Conclusions:

• The total synthesis of isokidamycin was successfully accomplished, marking a significant advancement.
• The developed synthetic methodology provides a powerful tool for accessing complex glycosides.
• This work opens avenues for the synthesis of other pluramycin analogues and related natural products.