School of Chemistry, University of Hyderabad, Gachibowli, Hyderabad-5000 046, Telengana, India.
Org Biomol Chem. 2020 Mar 11;18(10):1851-1876. doi: 10.1039/c9ob02765c.
The growing emphasis on macrocycles in engaging difficult therapeutic targets such as protein-protein interactions and GPCRs via preferential adaptation of bioactive and cell penetrating conformations has provided impetus to the search for de novo macrocyclization strategies that are efficient, chemically robust and amenable to diversity creation. An emerging macrocyclization paradigm based on the C-H activation logic, of particular promise in the macrocyclization of complex peptides, has added a new dimension to this pursuit, enabling efficacious access to macrocycles of various sizes and topologies with high atom and step economy. Significant achievements in macrocyclization methodologies and their applications in the synthesis of bioactive natural products and drug-like molecules, employing strategic variations of C-H activation are captured in this review. It is expected that this timely account will foster interest in newer ways of macrocycle construction among practitioners of organic synthesis and chemical biology to advance the field.
人们越来越重视大环化合物，通过优先适应生物活性和细胞穿透构象来结合蛋白质-蛋白质相互作用和 G 蛋白偶联受体等治疗靶点，这为寻找高效、化学稳定且易于产生多样性的新型大环化合物环化策略提供了动力。一种新兴的大环化范例基于 C-H 活化逻辑，在复杂肽的大环化中特别有前景，为这一探索增添了新的维度，使人们能够有效地获得各种大小和拓扑结构的大环化合物，具有高原子经济性和步骤经济性。本文综述了在生物活性天然产物和类药分子的合成中，采用 C-H 活化的策略变化，在大环化合物方法学及其应用方面取得的重大进展。预计这一及时的报道将激发有机合成和化学生物学领域的从业者对大环化合物构建的新方法产生兴趣，从而推动该领域的发展。
