Nine-step total synthesis of (-)-strychnofoline

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Natural Products Chemistry

Background:

• Strychnofoline, a Strychnos alkaloid, exhibits significant anticancer properties.
• Its unique spirooxindole architecture presents a synthetic challenge.
• Access to strychnofoline and its analogs is crucial for exploring therapeutic potential.

Purpose of the Study:

• To report the first enantioselective synthesis of strychnofoline.
• To develop an efficient and concise synthetic route.
• To provide a platform for synthesizing related bioactive spirooxindole alkaloids.

Main Methods:

• A nine-step synthetic sequence starting from commercially available 6-methoxytryptamine.
• Catalytic asymmetric synthesis for constructing the spiro[pyrrolidine-3,3'-oxindole] core.
• Sequential transformation strategy for efficient motif construction.

Main Results:

• Successful enantioselective synthesis of strychnofoline achieved.
• The synthesis was completed in only nine steps.
• The developed route efficiently constructs the spirooxindole framework.

Conclusions:

• A novel and efficient enantioselective synthesis of strychnofoline has been established.
• The synthetic strategy is versatile for accessing other natural and synthetic spirooxindole analogs.
• This work facilitates further investigation into the therapeutic applications of these compounds.