Knight Brian J, Grigolo Thiago A, Tolchin Zachary A, Smith Joel M
Department of Medicinal Chemistry, Asha Therapeutics, 3802 Spectrum Blvd. Suite 146, Tampa, FL, 33612, USA.
Department of Chemistry and Biochemistry, Laboroatories of Molecular Recognition, Florida State University, 95 Chieftan Way, Tallahassee, FL, 32308, USA.
Chemistry. 2025 Apr 1;31(19):e202402413. doi: 10.1002/chem.202402413. Epub 2025 Mar 4.
Since antiquity, alkaloid natural products have served as medicinal ingredients that still contribute as an inspiration for the development of novel therapeutics. For the synthetic chemist, much of the importance of natural products lies in their acting as a forcing-function for the invention of new synthetic strategies and tactics for molecular assembly. With this rich history in mind, it remains an important goal for chemists to build nitrogenous structures with greater efficiency, abiding by economies of synthesis. Nitrogenous aromatic feedstocks have been an intriguing starting point for the functionalization and construction of alkaloids for several decades, but recent advances in reaction design have opened new doors for leveraging their abundance in concise synthesis. Herein, advances in this area of synthetic ingenuity will be summarized with the aim of instructing chemists towards considering dearomatization as a strategic avenue for both target-oriented and diversity-oriented synthetic campaigns. Overall, syntheses are evaluated, compared, and contrasted to give a systematic overview of this continued area of research.
自古以来，生物碱天然产物一直作为药用成分，至今仍为新型治疗药物的开发提供灵感。对于合成化学家而言，天然产物的重要性很大程度上在于它们作为一种驱动力，促使人们发明新的分子组装合成策略和战术。鉴于这段丰富的历史，化学家的一个重要目标仍是更高效地构建含氮结构，遵循合成经济性原则。几十年来，含氮芳香原料一直是生物碱功能化和构建的有趣起始点，但反应设计方面的最新进展为在简洁合成中利用其丰富性打开了新的大门。在此，将总结这一合成创新领域的进展，旨在指导化学家将去芳构化视为目标导向和多样性导向合成活动的战略途径。总体而言，对各种合成方法进行评估、比较和对比，以系统概述这一持续的研究领域。
