Total Synthesis of Darobactin A
Total Synthesis of Darobactin A
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DOI：
10.1021/jacs.2c05891
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发表时间：
2022-07-28
影响因子：
15
通讯作者：
Sarlah, David
中科院分区：
文献类型：
--
作者：
Nesic, Marko;Ryffel, David B.;Sarlah, David
darobactin A 是一种最近分离的选择性靶向革兰氏阴性菌的抗生素，其协作全合成是由 D-Garner 醛和 L-丝氨酸以收敛方式完成的，最长线性序列为 16 个步骤。开发了三种非规范氨基酸的可扩展路线以实现合成。双大环的闭合是通过连续的、卤素选择性的 Larock 吲哚合成实现的，其中正确的环化顺序被证明对于天然产物所需阻转异构体的形成至关重要。
The collaborative total synthesis of darobactin A, a recently isolated antibiotic that selectively targets Gram-negative bacteria, has been accomplished in a convergent fashion with a longest linear sequence of 16 steps from D-Garner's aldehyde and L-serine. Scalable routes toward three non-canonical amino acids were developed to enable the synthesis. The closure of the bismacrocycle was realized through sequential, halogen-selective Larock indole syntheses, where the proper order of cyclizations proved crucial for the formation of the desired atropisomer of the natural product.