Which methods are used for synthesis of synthetic hits?

• A. Fermentation and biocatalysis
• B. Conventional synthesis of small molecules and combinatorial chemistry technology
• C. Extraction from natural products
• D. Genetic engineering only

Answer: (B)

Generating synthetic hits relies on two main approaches: traditional chemical synthesis of small molecules and combinatorial chemistry to create large, diverse libraries. Traditional synthesis lets chemists build a defined scaffold with systematic substitutions to probe how changes affect activity. Combinatorial chemistry uses parallel or split-and-pool techniques to rapidly produce hundreds to thousands of related compounds, expanding chemical space and increasing the chance of finding active hits. Other methods like fermentation/biocatalysis, extraction from natural products, or genetic engineering play important roles in producing compounds or enabling biosynthetic routes, but they are not the primary means for generating the broad, library-scale synthetic hits used in early discovery.