Extensively stereodiversified scaffolds for use in diversity-oriented library synthesis

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Stereodiverse compound libraries are crucial for drug discovery and chemical biology.
• Developing novel scaffolds that allow for independent variation of stereocenters is essential for exploring chemical space.
• Existing methods may not fully capture the geometric diversity required for comprehensive screening.

Purpose of the Study:

• To report the synthesis of novel stereodiverse compound libraries based on scaffolds 12 and 19.
• To demonstrate the utility of these scaffolds in diversity-oriented synthesis (DOS).
• To showcase the incorporation of these building blocks into peptide sequences.

Main Methods:

• Synthesis of N-Fmoc-amino acid derivatives (12 and 19) with multiple, independently varied stereocenters.
• Functionalization of the synthesized scaffolds.
• Incorporation of the functionalized scaffolds into peptide sequences.

Main Results:

• Successful synthesis of stereodiverse libraries of compounds 12 and 19.
• Each asterisk denotes an independently modifiable stereocenter, enabling geometric diversity.
• Demonstrated utility of scaffolds 12 and 19 as versatile building blocks in DOS via peptide incorporation.

Conclusions:

• Scaffolds 12 and 19 are valuable templates for generating stereochemically rich compound libraries.
• These building blocks facilitate the exploration of geometric diversity in library synthesis.
• The successful incorporation into peptides highlights their applicability in constructing complex molecules for further investigation.