Quaternary-centre-guided synthesis of complex polycyclic terpenes

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Quaternary centres, carbons bonded to four other carbons, significantly impact molecular chemistry and biology.
• They can enable challenging reactions, enhance drug properties like activity and metabolic stability, and direct selectivity in catalysis.
• However, their steric bulk often complicates synthesis, requiring specialized methods for their formation.

Purpose of the Study:

• To introduce a novel synthetic planning strategy that leverages quaternary centres to simplify subsequent chemical transformations.
• To demonstrate an efficient, scalable, and modular approach to synthesizing complex molecules containing multiple quaternary centres.

Main Methods:

• Designing synthetic routes where each quaternary centre facilitates the construction of the next.
• Utilizing rate acceleration and blocking effects conferred by quaternary centres.
• Applying this strategy to the synthesis of the conidiogenone family of terpenes.

Main Results:

• The developed strategy enables highly efficient and scalable syntheses.
• This approach simplifies the construction of complex molecular architectures.
• The conidiogenone family of terpenes was synthesized as a representative example.

Conclusions:

• A new synthetic planning logic based on the strategic use of quaternary centres has been established.
• This framework offers a powerful alternative for tackling complex syntheses involving multiple quaternary centres.
• The approach is broadly applicable to other targets of similar synthetic complexity.