Total Synthesis of Complex Biosynthetic Late-Stage Intermediates and Bioconversion by a Tailoring Enzyme from Jerangolid Biosynthesis.
Total Synthesis of Complex Biosynthetic Late-Stage Intermediates and Bioconversion by a Tailoring Enzyme from Jerangolid Biosynthesis.
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DOI：
10.1021/acs.joc.8b02047
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发表时间：
2018-10
期刊：
影响因子：
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通讯作者：
Frederick Lindner;Steffen Friedrich;F. Hahn
中科院分区：
文献类型：
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作者：
Frederick Lindner;Steffen Friedrich;F. Hahn
提出了一种高度收敛的途径，以获得生物合成的晚期中间体ProJerangolid和Jerangolid E，并通过合成新的非天然Jerangolid衍生物证明了其用途。关键步骤是通过Julia-Kocienski烯化和烯烃交叉复分解进行片段偶联，以及通过分子内oxa-Michael加成生成立体选择性的四氢吡喃。用定制的O-甲基转移酶Jerf进行的生物转化实验证实了它的生物合成作用，并揭示了该酶的底物专一性以及对有机共溶剂的耐受性。
A highly convergent access to the late-stage biosynthetic intermediates projerangolid and jerangolid E is presented, and its utility is demonstrated by the synthesis of novel non-natural jerangolid derivatives. The key steps are fragment couplings by Julia-Kocienski olefination and olefin cross metathesis, as well as a stereoselective tetrahydropyran formation by intramolecular oxa-Michael addition. Bioconversion experiments with the tailoring O-methyltransferase JerF confirmed its proposed biosynthetic role and revealed relaxed substrate specificity of this enzyme as well as tolerance to organic cosolvents.