Assessment of structural diversity in combinatorial synthesis

Area of Science:

• Medicinal Chemistry
• Synthetic Chemistry
• Computational Chemistry

Background:

• Natural products offer molecular diversity but have limitations for drug discovery.
• Diversity-oriented synthesis (DOS) aims to efficiently create structurally complex small molecules.
• High-throughput screening (HTS) requires diverse compound libraries for identifying drug leads.

Purpose of the Study:

• To review recent advancements in diversity-oriented synthesis for generating maximal structural diversity.
• To discuss strategies and molecular descriptors for assessing compound diversity.
• To evaluate software tools for quantifying structural diversity in combinatorial synthesis.

Main Methods:

• Literature review of diversity-oriented synthesis strategies.
• Analysis of molecular descriptors used in diversity assessment.
• Testing and evaluation of freely available web-based software for assessing structural diversity.

Main Results:

• Recent progress in DOS has enabled the efficient synthesis of diverse small molecules.
• Specific strategies and molecular descriptors are crucial for maximizing structural diversity.
• The tested software provides a valuable tool for assessing and comparing the diversity of synthesized compound libraries.

Conclusions:

• Combinatorial synthesis, particularly DOS, is vital for generating diverse compound libraries for drug discovery.
• Objective assessment of structural diversity using computational tools is essential for optimizing synthetic strategies.
• The reviewed software facilitates the evaluation of compound library diversity for HTS applications.