二萜合酶标记底物的设计与合成

发布时间：2018-05-01 12:33

本文选题：二萜合酶 + 酶环化反应　；参考：《化学试剂》2017年12期

【摘要】：从二萜类天然产物Cyclooctatin的环化机理猜想出发,设计[2-2H]GGDP(GGDP:香叶基香叶基焦磷酸)、[9-2H2]GGDP、[14-2H]GGDP等氘代底物,以供研究二萜合酶环化反应机理,并设计[2-F]GGDP氟代底物用于与酶的共结晶研究,以验证猜想的正确性。均以反式-反式金合欢醇为起始原料,分别利用乙酰乙酸甲酯双负离子和单负离子偶联的方法实现碳链的延长,完成了[2-2H]GGDP和[2-F]GGDP的合成工作。在[2-2H]GGDP合成中,β-酮酸酯经D2O交换在C-2位引入氘原子;在[2-F]GGDP合成中,与乙酰乙酸甲酯单负离子偶联后经Krapcho脱羧反应和Horner-WadsworthEmmons反应在C-2位引入F原子。该研究为[9-2H2]GGDP、[14-2H]GGDP的合成积累了经验,也为后续进一步研究酶环化反应机制奠定了基础。
[Abstract]:Based on the cyclization mechanism of diterpene natural product Cyclooctatin, deuterium substrates, such as [2-2H] GDPGDP: germanic pyrophosphate, [9-2H2] GGDPand [14-2H] GGDP, were designed for the study of cyclization mechanism of diterpene synthase, and the [2-F] GGDP fluorinated substrate was designed for the study of co-crystallization with enzymes. To verify the correctness of the conjecture. The carbon-chain was prolonged by coupling methyl acetoacetate with dianion and single anion, and the synthesis of [2-2H] GGDP and [2-F] GGDP were completed. In the synthesis of [2-2H] GGDP, deuterium atoms are introduced into 尾 -ketoate by D2O exchange at C-2, and in [2-F] GGDP synthesis by Krapcho decarboxylation and Horner-WadsworthEmmons reaction. This study has accumulated experience for the synthesis of [9-2H2] GDP, [14-2H] GGDP and laid a foundation for further study on the mechanism of enzymatic cyclization.
【作者单位】：漯河医学高等专科学校药学系;新乡医学院纳米生物医用材料重点实验室;河南大学天然药物与免疫工程重点实验室;
【基金】：河南省基础与前沿技术研究计划项目(1523-00410178) 高校博士科研基金资助项目(2014-DF-003)
【分类号】：O629.61

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