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手性輔助試劑2-硫基-4-苯基噻唑的合成研究及在不對稱羥醛縮合反應中的應用

時間:2019-04-12 21:07來源:畢業論文
基于Largazole和FK228的結構設計了一類新的環肽類HDAC抑制劑所需要的一個片段的合成.主要是一種新的手性輔基的合成及在不對稱羥醛縮合反應中的應用

摘要組蛋白乙酰轉移酶(histone acetykransferase,HAT)和組蛋白去乙酰酶(histone deacetylase,HDAC)通過對組蛋白氮端氨基酸殘基進行乙酰化或去乙酰化,調節組蛋白的乙酰化水平,調控基因表達,該過程與癌癥的發生具有密切的關系。組蛋白去乙酰酶抑制劑通過增加細胞內組蛋白的乙酰化程度,提高p21等基因的表達水平等途徑,抑制腫瘤細胞的增殖,誘導細胞分化和(或)凋亡。
Largazole是選擇性抑制I型HDAC的環肽類天然產物,且對腫瘤細胞和正常細胞具有顯著的選擇性。本論文基于Largazole和FK228的結構設計了一類新的環肽類HDAC抑制劑所需要的一個片段的合成.主要是一種新的手性輔基的合成及在不對稱羥醛縮合反應中的應用.34424
手性化合物在醫藥和材料科學等領域中被廣泛應用,其合成越來越受到重視。
在眾多有機小分子催化劑中,惡唑烷酮類手性輔基是不對稱合成中使用成功且應用最為廣泛的一類手性輔基。然而,以手性噻唑啉為母體的手性輔基,還沒有廣泛的開發和利用。所以對手性噻唑啉化合物進行結構修飾和改造,開發一類新型手性催化劑具有重要意義。因此,本文首先以 L-苯甘氨酸為基礎,圍繞Largazole合成中所需要的輔基,通過引入不同的官能團,對其進行修飾與改造,合成了Evans噻唑硫酮類手性輔基。
L-苯甘氨酸經酯化高收率還原成L-苯甘氨醇,在KOH水溶液中與CS2環合生成2-硫酮-4-苯基噻唑,產率81%
2-硫酮-4-苯基噻唑經過酰化得到2-硫酮3-乙酰基-4-苯基噻唑
圍繞Largazole合成中所需重要片段利用2-硫酮3-乙酰基-4-苯基噻唑進行不對稱羥醛縮合反應得到手性目標片段
畢業論文關鍵詞:Evans輔基;噻唑硫酮;手性合成;不對稱羥醛縮合反應 源`自*六)維[論*文'網www.aftnzs.live
ABSTRACT
Histone acetyltransferases (HAT) and histone deacetylases (HDACs) as the corresponding enzymes regulate the change of histones in two antagonist forms , acetylated or deacetylated. The histone deacetylases inhibitors (HDACIs) are potent inducers of growth arrest , differentiation and apoptosis of tumor cells , and have entered clinical trials for both solid and liquid tumors. However , the molecular basis for their anticancer selectivity remains largely unknown. An improved understanding of the structure and action mechanism of HDAC inhibitors will likely accelerate the clinical development and broaden the future scope and utility of HDAC inhibitors for cancer treatment .
Largazole is a natural cyclic peptide which can selectively inhibit Class I histone deacetylase and show remarkable selectivity between transformed and nontransformed cells. In this paper,we Designed and synthesized a new class of synthetic cyclic peptide HDAC inhibitors need a clip. The main is a new synthesis of chiral auxiliary group, and in the asymmetric aldol reaction of applications.
Chiral compounds are widely used in medicine and materials science and other fields, Oxazolidinone, thiophene thione, oxazolidine thione and camphor derivatives, such as chiral auxiliary reagents are widely used in the induction of asymmetric aldol condensation reaction, to obtain good asymmetric induction effect. So chiral compounds thiazoline structural modification and transformation, the development of a novel class of chiral catalysts is important. Therefore, this paper first to L- phenylglycine based around Largazole synthesis cofactor required, by introducing different functional groups, its modification and transformation, thiazole synthesis Evans chiral auxiliary Thiones L- phenylglycine reduced to high yield via esterification L- Phenylglycine alcohol, in aqueous KOH solution and CS2 cyclization to produce 2-thione-4-phenyl-thiazole, 81% yield
2- thione-4-phenyl-thiazol-acylation to give 2-thione 3-acetyl-4-phenyl-thiazole

源`自*六)維[論*文'網www.aftnzs.live


Around Largazole synthesis required the use of 2- thione important sequences 3-acetyl-4-phenyl-thiazole-asymmetric aldol reaction of chiral target fragment 手性輔助試劑2-硫基-4-苯基噻唑的合成研究及在不對稱羥醛縮合反應中的應用:http://www.aftnzs.live/huaxue/20190412/31919.html
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