Synthesis of sp(3)-rich scaffolds for molecular libraries through complexity-generating cascade reactions

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Developing efficient synthetic routes is crucial for accessing novel chemical entities.
• Complex small molecules are vital for drug discovery and development.
• Existing synthetic methods may lack the efficiency or scope required for large-scale compound production.

Purpose of the Study:

• To present an efficient synthetic strategy for complex small molecule synthesis.
• To demonstrate the utility of tandem Petasis and Diels-Alder reactions in a cascade sequence.
• To validate the methodology through the synthesis of a diverse compound set.

Main Methods:

• Utilizing tandem Petasis and Diels-Alder reactions.
• Employing divergent complexity-generating cyclization cascades.
• Synthesizing a key dialdehyde intermediate for further elaboration.

Main Results:

• Successful synthesis of a representative compound set.
• Demonstration of an efficient route from simple building blocks to complex molecules.
• Production of 1617 molecules for the European Lead Factory.

Conclusions:

• The presented strategy offers an efficient approach to complex small molecule synthesis.
• The methodology is robust and scalable, suitable for library generation.
• This work facilitates the discovery of new drug candidates through the European Lead Factory.