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摘要：不同光学活性的环戊烯酮衍生物是一类重要的有机合成中间体，在手性药物和天然产物合成方面都具有广泛的应用价值。鉴于多数环戊烯酮分子是具有手性的，然手性分子的一对对映异构体中往往只有一个对映体是具有生理效应的，而另一个对映体则是无效的，甚至对人体是有害的，对映体的分离成为了当前研究的一个热点。酶催化动力学拆分技术作为一种绿色高效的手段，具有对映选择性高、反应条件温和等优点，对于获得光学纯的化合物则发挥着不容小觑的作用。为了获得光学纯的2,4-二取代-2-环戊烯酮，本课题主要以2-呋喃甲醛为初始原料，利用格氏试剂加成得到1’-甲基-2-羟甲基呋喃，再先后通过Piancatelli重排、酶拆分、上保护基、Michael加成和消除等一系列反应。其中，本文着重研究了取代环戊烯酮的酶催化动力学拆分，并利用高效液相色谱监测反应拆分效果。同时就底物、温度、反应时间和酶介质的影响等进行了研究对比，确定了较佳的工艺条件，通过一系列的工艺优化最终确定了一条高收率低成本、操作简便，绿色环保且较为安全的工艺路线。结果表明，取代基为异丙基的底物在CAL-B酶催化条件下于常温下进行拆分时表现出较高的优越性，反应时间为16h，目标对映体含量达到94.44%，且该条件下的总收率最高，为36.02%。实验结果较为乐观并以1H核磁共振对产物进行了表征。33057
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毕业论文关键词：环戊烯酮；Piancatelli重排；动力学拆分
Enzymatic kinetic resolution of substituted cyclopentenones
Abstract：A series of representative optically active derivatives of cyclopentenones are a sort of important organic synthesis intermediates，with extensive application value in aspects of chiral pharmaceuticals and natural products. But most cyclopentenones are chiral. And only one enantiomer of the chiral molecule has physiological effect, while the other is noneffective, even harmful. The resolution of the enantiomers has become a hot research. The technology of enzymatic kinetic resolution, a green and efficient means with the advantage of high enantioselectivity, and mild reaction conditions, plays an important role in the synthesis of optically pure compounds. In order to obtain 1’-methyl-2-methylol furan, in this study, 2-formyl furan is utilized as the initial raw material to proceed an addition reaction with Grignard reagents. Then optically pure 2,4-disubstituted cylopentenones are finally synthesized via a series of reactions of Piancatelli rearrangement, enzymatic kinetic resolution, adding protecting groups, Michael addition and elimination. What’s more, the paper focuses on the preparation of substituted cyclopentenones and its enzymatic kinetic resolution. In the process, the effect of kinetic resolution is monitored by high performance liquid chromatography (HPLC). Simultaneously, a comparative study is also demonstrated among the influence of substrates, temperature, reaction time and enzymes, while an optimized process condition is determined. And though a series of optimization, a more secure and more environmentally friendly process route is ultimately determined, with the advantages of high yield, low cost and easy operation. The result demonstrates, when the substrate with iso-propyl is reacting in the catalysis of CAL-B under the regular temperature, it shows a high superiority. It takes 16h. And the condition is the best.The percentage of the target enantiomer is 94.44% and the total recovery is 36.02%。The result is relatively satisfactory and the products are characterized by 1H NMR.
Keywords：cyclopentenone；Piancatelli rearrangement；kinetic resolution
目 录
1 绪论 1
1.1 课题研究背景及意义 1
1.2 动力学拆分简介 3
1.3 动力学拆分的应用价值 3