Total Synthesis of the Broad-Spectrum Antibiotic Amycolamicin
Total Synthesis of the Broad-Spectrum Antibiotic Amycolamicin
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DOI：
10.1021/jacs.2c00647
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发表时间：
2022-03-30
影响因子：
15
通讯作者：
Kuwahara, Shigefumi
中科院分区：
文献类型：
--
作者：
Meguro, Yasuhiro;Ito, Junya;Kuwahara, Shigefumi
抗生素amycolamicin的全合成具有由五环系统组成的杂合分子结构，其对广泛的耐药细菌表现出有效的抗菌活性，已经以收敛的方式实现。一个无保护基的分子内Diels-Alder反应的羟基四烯醛中间体促进两个当量的Et 2AlCl，其中收益高度非对映选择性通过内赤道过渡态，已被用来构建的反式十氢萘部分的分子。通过北方N-糖苷单元（α-端基异构体/β-端基异构体= 1：1.1）与南方β-酮硫酯片段的完全立体会聚的N-酰化，然后安装中心特特拉姆酸部分，组装了Amycolamicin的完整结构。
The total synthesis of the antibiotic amycolamicin with a hybrid molecular architecture composed of five ring systems, which exhibits potent antibacterial activity against a wide range of drug-resistant bacteria, has been achieved in a convergent manner. A protecting-group-free intramolecular Diels-Alder reaction of a hydroxy tetraenal intermediate promoted by two equivalents of Et2AlCl, which proceeds highly diastereoselectively via an endo-equatorial transition state, has been utilized to construct the trans-decalin moiety of the molecule. The full structure of amycolamicin was assembled by a completely stereoconvergent N-acylation of a northern N-glycoside unit (alpha-anomer/beta-anomer = 1:1.1) with a southern beta-keto thioester segment followed by installation of the central tetramic acid moiety.