A Facile Fmoc Solid Phase Synthesis Strategy To Access Epimerization-Prone Biosynthetic Intermediates of Glycopeptide Antibiotics
A Facile Fmoc Solid Phase Synthesis Strategy To Access Epimerization-Prone Biosynthetic Intermediates of Glycopeptide Antibiotics
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DOI：
10.1021/ol500840f
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发表时间：
2014-05-02
期刊：
影响因子：
5.2
通讯作者：
Cryle, Max J.
中科院分区：
文献类型：
--
作者：
Brieke, Clara;Cryle, Max J.
描述了一种基于Fmoc化学的快速固相肽合成法合成万古霉素和替考拉宁型肽。通过优化的Fmoc-脱保护和偶联条件抑制高度外消旋倾向的芳基甘氨酸衍生物的差向异构化。从易于获得的Fmoc保护的氨基酸开始，该策略能够以优异的纯度和高产率（38%-71%）对映选择性合成对应于万古霉素和替考拉宁生物合成中发现的中间体的肽。
A rapid protocol based on Fmoc-chemistry for the solid phase peptide synthesis of vancomycin- and teicoplanin-type peptides is described. Epimerization of highly racemization-prone arlyglycine derivatives is suppressed through optimized Fmoc-deprotection and coupling conditions. Starting from easily accessible Fmoc-protected amino acids, this strategy enables the enantioselective synthesis of peptides corresponding to intermediates found in vancomycin and teicoplanin biosynthesis with excellent purity and in high yields (38%-71%).