通过β-羟基天冬氨酸连接介导的环化反应实现 Malacidin A 的全合成及其绝对结构确定。
Total Synthesis of Malacidin A by β-Hydroxyaspartic Acid Ligation-Mediated Cyclization and Absolute Structure Establishment.
机构信息
Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong, SAR, 999077, P. R. China.
Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, 10065, USA.
出版信息
Angew Chem Int Ed Engl. 2020 Nov 2;59(45):19868-19872. doi: 10.1002/anie.202009092. Epub 2020 Aug 31.
Abstract
The development of novel antibiotics is critical to combating the growing emergence of drug-resistant pathogens. Malacidin A is a new member of the calcium-dependent antibiotic (CDAs) family with activity against antibiotic-resistant pathogens. Its mode of action is distinct from classical CDAs. However, the absolute structure of malacidin A has not been established. Herein, the total syntheses of malacidin A and its analogues are reported by a combination of Fmoc-based solid-phase peptide synthesis (SPPS) and β-hydroxyaspartic acid ligation-mediated peptide cyclization. The total synthesis enabled us to establish the absolute configuration of malacidin A, which is in agreement with those for natural malacidin A confirmed by advanced Marfey's analysis in our study.
摘要
新型抗生素的开发对于对抗日益出现的耐药病原体至关重要。Malacidin A 是一种新型钙依赖性抗生素 (CDAs) 家族成员，对具有抗药性的病原体具有活性。其作用模式与经典的 CDAs 不同。然而，Malacidin A 的绝对结构尚未确定。在此，通过 Fmoc 固相肽合成 (SPPS) 和 β-羟基天冬氨酸连接介导的肽环化的组合，报道了 Malacidin A 及其类似物的全合成。该全合成使我们能够确定 Malacidin A 的绝对构型，与我们研究中通过高级 Marfey 分析确定的天然 Malacidin A 的绝对构型一致。
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