Diversity-oriented synthesis has historically focused on the generation of small-molecule collections with considerable scaffold, stereochemical, and appendage diversity. Recently, this focus has begun to shift to the production of small-molecule libraries with diverse biological activities. It is currently not clear which properties and structural features of molecules are predictive of diverse performance in biological assays, and a better understanding of this relationship is critical for the development of performance-diverse small-molecule libraries for the discovery of novel probes for challenging targets. This review explores recent synthetic strategies for the production of bioactive small molecules and concludes with a presentation of current methods that enable the assessment of the biological performance diversity of small-molecule libraries.

中文翻译：

---

面向下一代多样性的综合：从化学多样性到生物多样性的范式转变

过去，面向多样性的合成一直集中在具有大量支架，立体化学和附属物多样性的小分子集合的产生上。最近，这一重点已开始转移到具有多种生物活性的小分子文库的生产上。目前尚不清楚分子的哪些特性和结构特征可预测生物测定中的各种性能，并且对这种关系的更好理解对于开发性能多样的小分子文库以发现具有挑战性的靶标的新型探针至关重要。