Figure 1.

Comparison of diversity-oriented synthesis (DOS) and focused library synthesis (FLS). a, The goal of DOS is to create collections of compounds that are maximally diverse, thereby increasing the probability that different proteins will be targeted by different compounds in the library. In the example shown, Burke et al⁶⁵ created a library of compounds with different core structures (skeletons) starting from a common set of precursors (left). The six compounds on the right have different connectivity and are likely to interact with different proteins. b, The goal of FLS is to create analogues of the same core structure to optimize binding to a target or class of targets. If the compounds created are too diverse, they may lose their propensity to interact with the designated target protein. In this example, Sodeoka et al¹⁵ created a collection of acyltetronic acids that act as phosphate mimetics and so are likely to inhibit phosphatases. Their synthesis resulted in a library of compounds that are identical except for the portion highlighted in orange.