A three-component coupling approach to the ACE-ring substructure of C19-diterpene alkaloids

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• C19-diterpene alkaloids possess significant pharmacological activities.
• These complex molecules feature a fused hexacyclic ABCDEF-ring system.
• Efficient synthetic routes are crucial for accessing these valuable compounds.

Purpose of the Study:

• To develop an expeditious strategy for assembling the ACE-ring substructure of C19-diterpene alkaloids.
• To establish a key intermediate for the total synthesis of these natural products.

Main Methods:

• A three-component coupling strategy was employed.
• A radical-polar crossover reaction involving an AE-ring radical precursor, a C-ring radical acceptor, and an aldehyde was utilized.
• The reaction was mediated by triethylborane (Et3B) and oxygen (O2).

Main Results:

• The ACE-ring substructure (4a) was rapidly assembled.
• Three new stereocenters were successfully installed.
• The carbon chain corresponding to the B-ring was extended.
• The intermediate 4a contains the required C4,11-quaternary and C10-tertiary carbons.

Conclusions:

• The developed three-component coupling strategy provides an efficient route to the ACE-ring substructure.
• The synthesized ACE-ring intermediate is well-positioned for the construction of complete C19-diterpene alkaloid frameworks.
• This method advances the synthetic accessibility of pharmacologically relevant diterpene alkaloids.