硫色烯類衍生物的合成及應用

Abstract

苯並噻喃衍生物是重要且常見的主體結構，其不僅已被廣泛的用於醫藥、有機合成中間體、功能性材及染料合成的中間體料等方面，更表現出獨特的生物活性，吸引許多的科學家投入關於苯並噻喃衍生物的合成方法和相關藥物活性方面之研究。 本論文的研究分為兩大部分，第一部分是探討在室溫下以4-二甲氨基吡啶 (DMAP)，催化硫代乙酸酯與硝基苯乙烯進行分子間的1,4-麥可加成，能夠簡單且時間快速的合成出一系列高產率的硫色烯衍生物。 第二部分則是探討以一鍋化反應利用硫色烯衍生物做為起始物，再加入疊氮化鈉進行1,3-偶極環加成，可得到具有三氮唑雜環結構的中間產物，接著，加入1-氟-2-硝基苯及碳酸銫，在氧氣條件下進行芳香族親核性取代，即可獲得2,4,5-三取代的三唑產物。自從本世紀初“點擊化學”發明以來，疊氮產物已成為最重要的雜環化合物，大部分的1,2,3-三唑衍生物，不僅顯示出多樣的抗癌、抗發炎和抗菌等活性，也常被用來作為合成天然物的骨架。在此，我們提供了一種有效率且高產率合成三唑結構的方法，期望未來能廣泛應用於有機合成領域上。The dissertation is divided into two parts summarizing the results based on the experimental works performed during the course of study. The first part includes a convenient procedure for the synthesis of Benzothiopyran (thiochromene) derivatives via the Michael addition of sodium salt of (2-formylphenyl) ethanethioate and nitrostyrene in the presence of 4-Dimethylaminopyridine (DMAP) as catalyst one pot. Benzothiopyran (thiochromene) derivatives are important and ubiquitous motif structure which is present in wide variety of pharmaceuticals, synthetic intermediates, and functional materials. Besides that some of the Benzothiopyran (thiochromene) derivatives acts as dyes. Thus, Benzothiopyran derivatives have triggered sustainably increasing attention in the synthetic and medicinal chemistry communities. The second part describes a successful route for the one-pot two-step sequence involving a nucleophilic aromatic substitution (SNAr) of activated fluorobenzenes with azide nucleophile and in situ Huisgen cycloaddition of the resulting sodium azides with thiochromenes has been developed for a rapid access to 2,4,5-trisubstituted 1,2,3-(NH)-triazoles. Most of the 1,2,3-triazole derivatives shows anticancer activities, anti-inflammatory and antimicrobial, etc. Also often used as a backbone in the synthesis of natural products. Here, we provide an efficient and high yield method for the synthesis of triazole structure.