Total synthesis of (+/-)-chartelline C

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Heterocyclic Chemistry

Background:

• Chartelline C is a complex natural product with a challenging molecular structure.
• Previous efforts to synthesize chartelline C have been unsuccessful, leaving its total synthesis as a long-standing challenge.

Purpose of the Study:

• To report the first concise total synthesis of (+/-)-chartelline C.
• To develop and showcase novel synthetic methodologies applicable to complex heterocyclic compounds.

Main Methods:

• A 10-step synthetic sequence was designed and executed.
• Key steps included chemo- and position-selective halogenation, selective alkyne reduction, and a facile vinyl carboxylic acid thermolysis.
• A novel ring contraction strategy was employed for the final heterocyclic core construction.

Main Results:

• The first total synthesis of (+/-)-chartelline C was successfully completed.
• The synthesis demonstrated efficient installation of heteroaromatic halogens and a sensitive beta-chloroenamide moiety.
• A unique ring contraction proved effective, highlighting its potential for broader heterocyclic synthesis.

Conclusions:

• The developed 10-step route represents a significant advancement in the synthesis of complex alkaloids.
• The novel methodologies, particularly the ring contraction, offer valuable tools for future heterocyclic chemistry research.
• This synthesis opens avenues for further investigation into the biological activities and structural analogs of chartelline C.