利用「骨牌式反應」合成「吡喃-2-酮」、「α-胺基酸」、「脫氧醣」以及設計與製備具含生物活性之「奈米球」

巴來吉

山西大学，您好！

感谢采购，人社期刊库｜人社论文库，期间：2025/01/01~2025/12/31

感谢试用，科学期刊库｜科学论文库，期间：2024/10/20~2025/01/20

浏览高级检索

关闭
检索检索高级检索出版物检索
浏览期刊主题浏览核心期刊浏览期刊拼音浏览

关闭

查询符号(半角)	查询符号意义说明
空格	表示为「AND」两个查询词之交集
双引号 ( " " )	片语以双引号标示开始及结束，而且只寻找出现顺序相同的字词，例： " image process "
?	表示一个字母切截，输入两个?表两个字母，依此类推，例：输入「Appl?」，查得结果应为appl e , appl y … ( 常用于英文字查询 )
*	表示不限字母切截，由0~n. 例：输入「appl*」，查得结果应为appl e , appl es , appl y , appl ied , appl ication … ( 常用于英文字查询 )
AND、OR、NOT	布尔逻辑组合关键字，用来扩大或缩小查询范围的技巧。 (1) AND ：缩小查询范围 (2) OR ：扩大查询范围(3) NOT：排除不相关的范围

DOI 是数位物件识别码（ D igital O bject I dentifier ）的简称，
为物件在网路上的唯一识别码，可用于永久连结并引用目标物件。

使用DOI作为永久连结

每个DOI号前面加上「 http://dx.doi.org/ 」便成为永久网址。
如以DOI号为 10.5297/ser.1201.002 的文献为例，此文献的永久连结便是： http://dx.doi.org/ 10.5297/ser.1201.002 。
日后不论出版单位如何更动此文献位置，永久连结所指向的位置皆会即时更新，不再错失重要的研究。

引用含有DOI的文献

有DOI的文献在引用时皆应同时引用DOI。若使用APA、Chicago以外未规范DOI的引用格式，可引用DOI永久连结。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。

书目管理工具

相关连结

问题回报

全文下载

利用「骨牌式反应」合成「吡喃-2-酮」、「α-胺基酸」、「脱氧醣」以及设计与制备具含生物活性之「奈米球」

Domino reactions in the Syntheses of Chroman-2-ones, α-Amino Acids, and Deoxy Sugars as well as Preparation of Nano-Bullets containing Biologically Active Compounds

巴来吉 , 博士　　导师：胡纪如　　

英文

利用「骨牌式反应」合成；吡喃-2-酮； α-胺基酸；脱氧醣； Domino reactions ； chroman-2-one ； 2-deoxy sugars ； nano bullets

0 个人觉得这篇文章赞

摘要 │ 参考文献 (161) │ 国际计量

摘要〈TOP〉

骨牌反应应用於合成苯并二氢吡喃、胺基酸及脱氧醣衍生物暨
含生物活性分子之奈米药用子弹
摘要
有机合成最重要的目标之一是将简单之化合物组装合成至较复杂之化合物。常用的步骤为一步接着一步完成目标分子内的键结；然而我们可以藉由在单一序列的反应上不纯化分离中间物、添加反应物、改变反应条件来提升效率。骨牌反应为一个不错的方法可以进行如此高效率的合成复杂化合物，藉由免除中间步骤之纯化与分离步骤来达到大程度的减少操作时间与开销。
许多胺基苯并二氢吡喃和胺基二芳基丙胺酸化合物拥有生物活性。於此，一个新的骨牌反应方法应用於高效率合成这些衍生物。首先将各式各样的酚、吖内酯及三氯化铝在甲苯以动力学控制反应於摄氏八十度产生预期的胺基苯并二氢吡喃，产率为百分之六十五至九十。这个在同一个反应瓶内发生的连结反应包含傅里德-克拉夫茨反应及後续的转酯反应。以其他路易士酸替换三氯化铝会无法得到同样的产物。接着，以小苏打进行水解胺基苯并二氢吡喃於四氢呋喃与水的混合溶液来得到α-(N-苯甲酰)胺基酸。
N端保护的α-胺基酸分子於蛋白质体学及合成化学领域上相当的有用，其上的羟基及羧基可以让他们接上其他核酸、胺基酸和药物分子。在接上之後，N端保护基可以去除以露出胺基。利用此特性，我们可以温和的方式从苯并二氢吡喃来合成N端保护的α-胺基酸，随後以盐酸甲醇溶液去除保护基来得到对应的α-胺基酸；产率分布於百分之八十至八十八之间。在优化的条件下，α-N-苯甲酰及α-胺基酸上的α-碳并未出现差向异构的现象。这些发现提供了一个非常好的方法来进行高度立体专一性地合成3、4取代的苯并二氢吡喃及二芳基丙胺酸衍生物。
脱氧醣为天然物中重要且丰富的的碳水化合物之一，其衍生物有相当多的生物功能，诸如抗生素及抗癌活性等等。在本研究中，我们以骨牌反应方法来将胺基醛醣及酮醣转化成脱氧醣，其中在温和反应中产生的苯炔来当作後续关键步骤的还原剂。胺基醛醣及酮醣与二硫化碳及乙酸酐反应而转化成对应的1,3-噻唑啉-2-硫酮，其上面的羟基全部都带有保护基。在关键的步骤中，这些噻唑啉-2-硫酮和2-(三甲基硅)苯基三氟甲烷磺酸盐及氟化铯於乙腈溶剂内进行常温反应生成非环状的烯醇乙酸酯。烯醇乙酸和甲醇中的甲醇钠进行皂化反应而在原位进一步发生分子内环化反应产生预期产物D-2-脱氧醣。在骨牌式还原去胺反应中的关键步骤中，1,3-噻唑啉-2-硫酮和苯炔之间发生[3+2]环加成反应之机构，接下来的偶极体进行逆[3+2]开环反应生成对应的烯醇乙酸酯。
标靶药物传递是一个输送药物分子的聪明的方法来提升药物到达病灶的浓度。利用奈米科技来产生奈米结构当作传输载具可以解决这方面的问题。金奈米粒子提供了相当棒的奈米载具供作合成鹰架，因为金奈米多才多艺、良好的生物相容性以及低毒性。另外，光提供了外部的刺激来打断可被光裂解的键结，这个反应可以应用於奈米载具的化学性应答。为了有选择性的瞄准癌症，我们开发了可同时对抗癌症及DNA切割弹头的奈米子弹。
抗癌药物接在可光解的连接分子上，并以共驾键结接着在金奈米粒子上。第二个连接分子带有季铵盐以离子键结抓取寡核苷酸并接着在金奈米粒子上。生成的奈米粒子都会经过後续分析，如紫外线光谱、电子显微镜、核磁共振光谱仪、红外线光谱仪以及表面电位量测。初步的光启动将金奈米粒子转化为抗癌症药物也已执行，光激发金奈米释放药物tegafur可以在紫外线光谱发现在272 nm有吸收波峰，而 tegafur的吸收最大波长274 nm。

三个主题会在论文内详细讨论。第一，一个新的骨牌反应方法应用於高效率合成胺基苯并二氢吡喃和胺基二芳基丙胺酸。第二，有活性的苯炔在原位生成并形成去胺反应的还原剂，此方法已成功应用於从胺基醛醣及酮醣合成脱氧醣之关键步骤。最後，发展含有生物活性分子之奈米子弹可以解决在许多疾病中久而未决的药物传输问题。

并列摘要〈TOP〉

Domino reactions in the Syntheses of Chroman-2-ones, α-Amino Acids, and Deoxy Sugars as well as Preparation of Nano-Bullets containing
Biologically Active Compounds
Dangeti Balaji Chandrasekhar
Abstract
One of the fundamental objectives of organic synthesis is the construction of complex molecules from simpler ones.  The usual procedure for the synthesis of organic compounds is stepwise formation of the individual bonds within the target molecule.  However, it would be much more efficient, if one can form several bonds in a single sequence without isolating the intermediates, changing the reaction conditions, or adding additional reagents.  Domino reactions allow such  highly efficient synthesis of complex organic compounds , as these processes take place without intermediate recovery steps, their use drastically reduces operating times and costs as well as the consumption of chemicals and  use of energy.
Many 3-aminochroman-2-ones and β,β-diarylalanines exhibit significant biological activities.  A new domino method was thus developed for the syntheses of these compounds with high efficiency.  First, treatment of various phenols with the Erlenmeyer–Plochl (Z)-azlactones and AlCl3 in toluene at 80 °C produced the desired cis-3-aminochroman-2-ones in 65–90% yields under kinetic control.  This coupling reaction involved  Friedel–Crafts alkylation followed by transesterification, which took place in a single-flask.  The same products could not be obtained by the replacement of AlCl3 with  protonic acid as the catalyst.  Second, hydrolysis of 3-amino-4-arylchroman-2-ones by NaHCO3 in a mixture of THF and water gave α-(N-benzoyl) amino acids.
The N-protected -amino acids area class of valuable compounds in proteomic and synthetic chemistry.  The free hydroxyl and carboxyl groups therein allow them to be coupled with nucleic acids, various drugs, and other amino acids.  Afterwards, the N-protected group can be removed to give free amines.  On the basis of this advantage, it encouraged us to find mild conditions for the generation of N-protected -amino acids from chroman-2-ones.  Deprotection of these isolated compounds with aqueous hydrogen chloride (12 N) and in methanol produced the corresponding free amino acids in 80–88% yields. Under these optimized conditions, epimerization did not occur at the α carbons of α-(N-benzoyl)- and free α-amino acids.  These new findings provide a convenient avenue of producing 3,4-disubstituted choman-2-ones and β, β-diarylalanines derivatives with very high steroselectivity.
Deoxy sugars constitute an important class of carbohydrates that occur widely in natural products, many of which exhibit antibiotics and anti-cancer activities as well as play versatile and essential biological roles.  A domino method was developed by using benzyne, generated under mild condition, as a reducing agent in the key step to convert amino sugars and ketoses to deoxy sugars.  By reacting with CS2 and then acetic anhydride, amino sugars and ketoses can be readily converted to the corresponding 1,3-thiazolidine-2-thiones with all hydroxyl groups therein protected.  In the key step, these thiazolidine-2-thiones were treated with 2-trimethylsilylphenyl triflate (2.0 equiv) and CsF (3.0 equiv) in acetonitrile at room temperature to produce acyclic enol acetates in good yields (51–63%).  Saponification of enol acetates with NaOMe in MeOH followed by intramolecular cyclization in situ gave the desired targets D-2-deoxy-sugars.  The key step in the domino reductive deamination involved a mechanism of [3+2] cycloaddition between benzyne and 1,3-thiazolidine-2-thione, followed by retro [3+2] ring opening of the resultant ylide to afford the corresponding enol acetate.
Targeted drug delivery is a smart method to deliver therapeutics in such a way to increase the concentration of the drug specifically only in some portions of the body.  The fundamental challenge in targeted drug delivery can be addressed with nanotechnology using nanostructures as delivery vehicles (nanocarriers).  Gold nanoparticles (Au NPs) provide an attractive synthetic scaffold for the creation of nanocarriers due to their functional versatility, better biocompatibility, and low toxicity.  Furthermore, light provide a highly orthogonal external stimulus and used to break photo-cleavable bonds to produce chemical responses from nanocarriers.  For the selective targeting of cancer, we developed nano-bullets capable of holding both an anticancer drug and DNA cleaving warhead with an oligonucleotide on a gold nanoparticle.
The anticancer drug was attached to a photo cleavable linker and hooked to gold nanoparticle through a covalent bond.  A second linker having tetrammonium salt for holding the oligonucleotide through ionic bond was prepared and attached to the gold nanoparticle.  The nano particle prepared were well characterized by using UV, TEM, 1H-NMR, IR and zeta potential.  Preliminary assessment of the light-triggered conversion of Au-NPs to anticancer drug was performed, Au-NPs with drug were displayed photoliberation to tegafur by observing a peak at 272 nm which is consistent with the UV absorption of tegafur at 274 nm.
Three major issues discussed in this dissertation, first, a new domino method was developed for the syntheses of 3-aminochroman-2-ones and β,β-diarylalanines with high efficiency.  Second, active benzyne generated in situ was developed as a reducing reagent for deamination.  This method was applied successfully as the key step in the synthesis of deoxy sugars in an optically active form from 2-amino sugars and 2-ketoses.  Alternatively, the development of nano-bullets containing biologically active compounds can efficiently resolve the long-lasting drug delivery problems in tackling various diseases. In addition, the conjugation of gold nanoparticles with oligonucleotide containing warhead groups are currently ongoing and the results will be reported in the near future.

参考文献 ( 161 ) 〈TOP〉

(2) Tietze, L. F. Chem. Rev. 1996, 96, 115–136.
连结：
(3) (a) Robinson, R. J. Chem. Soc. 1917, 111, 762–768. (b) Schöpf, C.; Lehmann, G.; Arnold, W. Angew. Chem. 1937, 50, 779–787.
连结：
(5) van Tamelen, E. E.; Hwu, J. R. J. Am. Chem. Soc. 1983, 105, 2490–2491.
连结：
(7) Swain, S. P.; Shih, Y.-C.; Jacob, J.; Tsay, S.-C.; Lin, C.-C.; Hwang, K. C.; Horng, J.-C.; Hwu, J. R. Angew. Chem. Int. Ed. Engl. 2015, 54, 9926¬–9930.
连结：
(10) Yao, C.-S.; Lin, M.; Wang, L. Chem. Pharm. Bull. 2006, 54, 1053–1057.
连结：

国际计量

〈TOP〉

E-mail ：

文章公开取用时，将寄通知信至您填写的信箱地址

E-mail ：

使用DOI作为永久连结

引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。