Function through synthesis-informed design.

Area of Science:

• Organic Synthesis
• Chemical Biology
• Molecular Design

Background:

• The field of organic synthesis has evolved significantly, with changing targets, methods, and goals.
• Traditionally, natural products dominated synthetic targets, but molecular design is increasingly important.
• Achieving molecular function with synthetic economy remains a central objective.

Purpose of the Study:

• To present a perspective on 21st-century synthesis, focusing on design and molecular function.
• To introduce and exemplify Function-Oriented Synthesis (FOS) as a strategy for achieving function through design.
• To highlight the shift from structure-based to function-based target identification and synthesis.

Main Methods:

• Function-Oriented Synthesis (FOS) approach, emphasizing initial target design based on desired function.
• Utilizing computational tools and chemical expertise for de novo structure creation.
• Retrofunction analysis to identify optimal synthetic targets based on function.

Main Results:

• Demonstrated FOS in molecular recognition, yielding designed kinase ligands and inhibitors.
• Developed simplified, functionally active photonucleases for DNA cleavage.
• Created cell-penetrating molecular transporters for drug delivery.
• Synthesized novel reagents for efficient cycloaddition reactions, enhancing structural complexity.

Conclusions:

• FOS offers a powerful strategy for designing and synthesizing molecules with specific functions.
• This approach allows for greater control over structure-function relationships and synthetic efficiency.
• Function-Oriented Synthesis represents a paradigm shift, where molecular form follows function.