Total Syntheses of Hosieines A-C

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Hosieines A-C are natural products with a complex cage-like tetracyclic structure.
• The total synthesis of these compounds presents a significant challenge in organic chemistry.

Purpose of the Study:

• To achieve the first total synthesis of hosieines B and C.
• To develop an efficient synthetic route towards hosieines A-C, establishing their complex tetracyclic framework.

Main Methods:

• A key one-pot domino reaction sequence was employed.
• This sequence involved copper-catalyzed [3+2] cycloaddition, 1,6-enone formation, and 1,6-aza-Michael addition.
• Further steps included a double bond migration and a 1,4-aza-Michael addition to complete the tetracyclic core.

Main Results:

• The collective total syntheses of (±)-hosieines A-C were successfully realized.
• This marks the first reported synthesis of hosieines B and C.
• The synthetic strategy efficiently constructed the intricate 5/6/6-aza-tricyclic and subsequent tetracyclic skeleton.

Conclusions:

• The developed synthetic strategy provides a viable route to hosieines A-C.
• This work demonstrates the power of domino reactions in constructing complex polycyclic natural products.
• The synthesis opens avenues for further exploration of hosieine derivatives and their potential biological activities.