Yi Sihyeong, Varun Begur Vasanthkumar, Choi Yoona, Park Seung Bum
Department of Chemistry, CRI Center for Chemical Proteomics, Seoul National University, Seoul, South Korea.
Front Chem. 2018 Oct 22;6:507. doi: 10.3389/fchem.2018.00507. eCollection 2018.
In the interdisciplinary research field of chemical biology and drug discovery, diversity-oriented synthesis (DOS) has become indispensable in the construction of novel small-molecule libraries rich in skeletal and stereochemical diversity. DOS aims to populate the unexplored chemical space with new potential bioactive molecules via forward synthetic analysis. Since the introduction of this concept by Schreiber, DOS has evolved along with many significant breakthroughs. It is therefore important to understand the key DOS strategies to build molecular diversity with maximized biological relevancy. Due to the length limitations of this mini review, we briefly discuss the recent DOS plans using build/couple/pair (B/C/P) and ring-distortion strategies for the synthesis of major biologically relevant target molecules like natural products and their related compounds, macrocycles, and privileged structures.
在化学生物学与药物发现这一跨学科研究领域，导向性多样性合成（DOS）在构建富含骨架和立体化学多样性的新型小分子文库过程中已变得不可或缺。导向性多样性合成旨在通过正向合成分析，用新的潜在生物活性分子填充未被探索的化学空间。自施赖伯引入这一概念以来，导向性多样性合成已随着诸多重大突破而不断发展。因此，了解构建具有最大生物学相关性的分子多样性的关键导向性多样性合成策略至关重要。由于本微型综述篇幅有限，我们简要讨论了近期使用构建/偶联/配对（B/C/P）和环扭曲策略来合成主要生物学相关靶分子（如天然产物及其相关化合物、大环化合物和特权结构）的导向性多样性合成方案。
