In the field of chemical biology, small molecules have been widely utilized for the elucidation of biological systems, named chemical genetic approaches. The chemical genetic approaches are allowed to uncover the bioactive small molecules and function-unknown proteins that can serve as the starting point for further medicinal chemistry investigations. Therefore, the quality of small molecule compound library determines the fate of biological research outcomes. In this article, we summarized advanced and frequently used approaches for the compound library synthesis. The classification of these approaches based on the logic of preparation. Besides, we also selected representative examples for each approach for the better understanding. Hopefully, this review article can provide a general view for the field, the ideal of application these approaches or the inspiration of developing novel small molecule library synthetic approach.
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