Liu Fan, Myers Andrew G
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Curr Opin Chem Biol. 2016 Jun;32:48-57. doi: 10.1016/j.cbpa.2016.03.011. Epub 2016 Apr 1.
Tetracyclines have proven to be safe and effective antibiotics over decades but to date all approved members of the class have been discovered and manufactured by chemical modification of fermentation products, which greatly limits the number of new structures that can be explored as future medicines. This review summarizes research leading to the development of a platform synthetic technology that enabled the discovery of the clinical candidate eravacycline, as well as other promising new tetracycline antibiotics, and provides the basis for a practical route for their manufacture. The approach argues for a reassessment of other antibiotic classes based on natural products for which practical, fully synthetic routes have not yet been developed, suggesting that these may represent underdeveloped resources with great potential to offer safer and more effective anti-infective agents.
几十年来，四环素已被证明是安全有效的抗生素，但迄今为止，该类所有已获批的成员都是通过对发酵产物进行化学修饰而发现和制造的，这极大地限制了可作为未来药物探索的新结构数量。本综述总结了导致开发一种平台合成技术的研究，该技术促成了临床候选药物依拉环素以及其他有前景的新型四环素抗生素的发现，并为其制造提供了一条实用路线的基础。该方法主张对基于天然产物的其他抗生素类别进行重新评估，因为尚未开发出实用的全合成路线，这表明这些可能代表着尚未充分开发的资源，具有提供更安全、更有效抗感染药物的巨大潜力。
