Total Synthesis of Strychnine

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Strychnine is a complex indole alkaloid derived from the Strychnos genus.
• Its intricate structure presents a significant challenge for total synthesis.
• Previous synthetic routes have been lengthy and less efficient.

Purpose of the Study:

• To achieve the total synthesis of strychnine.
• To develop a concise and efficient synthetic route.
• To demonstrate the application of asymmetric counterion-directed catalysis in target-oriented synthesis.

Main Methods:

• The synthesis employed a novel vinylogous 1,4-addition.
• Key steps included iodinium salt mediated silyl enol ether arylation and palladium-catalyzed Heck reaction.
• Asymmetric counterion-directed catalysis (ACDC) was utilized for enantioselective synthesis.

Main Results:

• The total synthesis of strychnine was successfully accomplished.
• A streamlined, late-stage conversion to the target molecule was developed.
• Optically active strychnine was accessed via ACDC, representing a significant advancement.

Conclusions:

• The described synthetic sequence is the most concise to date for optically active strychnine.
• This work provides a valuable new strategy for the synthesis of complex indole alkaloids.
• The application of ACDC highlights its utility in complex molecule synthesis.