有機連鎖反應1,6/1,4-加成製備多取代香豆素衍生物

Synthesis of Polysubstituted Coumarin Derivative via Organodomino 1,6/1,4-Addition

黃昱捷(Huang Yu-Jie)

指導教授 ： 陳焜銘

國立臺灣師範大學/理學院/化學系/碩士(2020年)

https://doi.org/10.6345/NTNU202001023

摘要

香豆素及其雜環衍生物表現出有益和多樣化的生物學活性，包括抗腫瘤，抗菌，抗炎，抑制人碳酸酐酶和抗癌活性。最常用來作為抗凝血劑使用。故香豆素衍生物的製備及應用的成為許多人研究合成的目標。也有許多合成應用的例子，本研究使用香豆素為主體的衍生物，做為同時具有親核性與親電性的化合物，與雙烯化合物在DABCO的催化下，以硝基苯為溶劑，在0 oC條件下進行反應。經由1,6-Michael/1,4-Michael連鎖反應得到產物，此產物具有五個連續的立體中心，在8個例子中，可得到中等智良好的產率（44-69%），非鏡像異構物比例達10.7：1。期望此策略能運用在天然物合成與藥物製成。加入掌姓催化劑進行不對稱合成，合成具有高光學純度的產物。

關鍵字

有機催化合成 ； 麥可加成 ； 有機連鎖反應 ； 香豆素 ； 苯磺醯基丁二烯

並列摘要

Coumarin and its heterocyclic derivatives exhibit beneficial and diverse biological activities, including anti-tumor, antibacterial, anti-inflammatory, human carbonic anhydrase inhibition, and anti-cancer activities. It is commonly used as an anticoagulant. Therefore, the preparation and application of coumarin derivatives has become the goal of many group's research and synthesis. There are also many examples of synthetic applications. In this study, coumarin-based derivatives were used as compounds with both nucleophilic and electrophilic properties, and diene compounds were catalyzed by DABCO with nitrobenzene as the solvent. The reaction was carried out at 0 oC. The product is obtained through the 1,6-Michael/1,4-Michael chain reaction. This product has five consecutive stereocenters. In 8 examples, a moderately good yield（44-69%）can be obtained, non-mirror image. The ratio of isomers reaches 10.7：1. It is expected that this strategy can be applied to the synthesis of natural products and the manufacture of medicines. Chiral catalysts are added for asymmetric synthesis to synthesize products with high optical purity.

並列關鍵字

Organocatalysis ； Michael Addition ； Domino Reaction ； Coumarin ； Phenylsulfonyl Butadiene

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