本文關(guān)鍵詞： 苯醌安莎霉素 Herbimycin A 熱休克蛋白90抑制劑 不對(duì)稱合成　出處：《北京協(xié)和醫(yī)學(xué)院》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：本論文介紹了一條兼具實(shí)用性與經(jīng)濟(jì)性的苯醌安沙霉素類天然產(chǎn)物的通用合成路線。 以Sharpless不對(duì)稱雙羥化反應(yīng)、Katuski不對(duì)稱環(huán)氧化反應(yīng)為關(guān)鍵步驟,構(gòu)建了苯醌安莎霉素類天然產(chǎn)物C8-C15部分的通用合成砌塊。利用Weinreb-CBS策略引入芳香片段,并構(gòu)建C15位手性中心。以市售手性源物質(zhì)為原料,經(jīng)7步簡(jiǎn)單的化學(xué)反應(yīng)合成了C1-C7片段。隨后,通過(guò)5步反應(yīng)實(shí)現(xiàn)了目標(biāo)分子的后期組裝工作；其中,借助于二甲基鋅介導(dǎo)的親核加成反應(yīng),立體選擇性地完成了片段連接。最終,經(jīng)19步線性步驟成功地完成了HerbimycinA的全合成,總收率為4.2%。 另一方面,憑借Weinreb-去羰基化策略,經(jīng)9步反應(yīng),構(gòu)建了GeldanamycinC11-C21片段,總收率為24%。證明了此路線系一條苯醌安沙霉素類天然產(chǎn)物的通用合成路線。 以上合成路線以催化的不對(duì)稱反應(yīng)代替了昂貴且敏感的手性試劑及原料；同時(shí),避免了因使用手性輔基而帶來(lái)的官能團(tuán)轉(zhuǎn)化步驟。此外,在后期階段引入芳環(huán)部分,實(shí)現(xiàn)了該類化合物的匯聚性合成。簡(jiǎn)捷的骨架構(gòu)建方法和靈活的手性中心建立策略,使我們有能力開(kāi)展關(guān)于苯醌安莎霉素類化合物的構(gòu)效關(guān)系研究以及結(jié)構(gòu)改造工作。
[Abstract]:This paper introduces a general synthetic route of benzoquinone anamycin natural products which is both practical and economical. The key step is Sharpless asymmetric double hydroxylation reaction and Katuski asymmetric epoxidation reaction. The general synthetic block of natural product of benzoquinone Ansanamycin C 8-C 15 was constructed and aromatic fragments were introduced by Weinreb-CBS strategy. The C _ 1-C _ 7 fragment was synthesized by a simple chemical reaction of seven steps, and the target molecule was assembled at a later stage by a five-step reaction, and the chiral center of C _ (15) was constructed. The chiral material was used as the raw material and the C _ 1-C _ 7 fragment was synthesized by a simple chemical reaction in 7 steps. The fragment ligation was accomplished stereoselective by dimethylzinc-mediated nucleophilic addition reaction. Finally, the complete synthesis of HerbimycinA was successfully completed through 19 step linear steps. The total yield was 4.2. On the other hand, the GeldanamycinC11-C21 fragment was constructed by 9 steps with Weinreb-decarbonylation strategy. The total yield is 24. It is proved that this route is a general synthetic route for the natural products of benzoquinone ansarcomycin. The above synthetic route replaces the expensive and sensitive chiral reagents and raw materials with catalytic asymmetric reactions. At the same time, the step of functional group transformation caused by the use of chiral cogroups is avoided. In addition, the aromatic ring is introduced at a later stage. The convergent synthesis of this kind of compounds, simple skeleton construction method and flexible chiral center establishment strategy have been realized. It enables us to study the structure-activity relationship and structural modification of benzoquinone Ansanamycin compounds.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5

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本文編號(hào)：1486745