【作者】 李文曲；

【导师】 李战雄；

【作者基本信息】 苏州大学 ， 纺织化学与染整工程， 2009， 硕士

【摘要】 氨基酸是构成蛋白质的基本单元,可应用于药物研发平台和手性药物生产。新型氨基酸及其衍生物合成一直以来是合成化学家们的研究热点。本文从廉价易得的氨基酸出发合成了一些新型氨基酸及其衍生物。主要内容包括两部分。以Ivdde作为保护基的氨基酸在蜘蛛毒素和锥虫杆毒素等多肽的合成中有很好的应用,本文以Ivdde对四种不同碳链长度的氨基酸Fmoc-Dap-OH、Fmoc-Dab-OH、Fmoc-Orn-OH和Fmoc-Lys-OH的末端氨基实行保护,分别合成得到了末端氨基Ivdde保护的氨基酸Fmoc-Dap(Ivdde)-OH、Fmoc-Dab(Ivdde)-OH、Fmoc-Orn(Ivdde)-OH和Fmoc-Lys(Ivdde)-OH。对四种氨基酸的反应性研究表明,得到的保护氨基酸的合成方法具有实用价值,适合于放大制备。对抗疗法非蛋白原氨基酸在诸如艾滋病毒蛋白酶抑制剂、凝血酶抑制剂等合成方面有着重要的作用,其中以3,(4)取代的焦性谷氨酸作为构成元的生物活性缩氨酸可给出关于受体识别和亲和度的更多信息。本文研究了将-s焦谷氨酸转化为OBO酯的合成方法。该邻酯官能群被用来作为针对1,4-铜酸盐和3,4-不饱和焦谷氨酸的芳烷基的立体选择性引入的控制团。经过去脱保护和开环处理之后,获得3取代的(2S,2S)-3-甲基谷氨酸。更多还原

【Abstract】 As the basic building block, amoni acid has received the wide attention of chemists. Just take the amoni acids and peptides used nowadays for the drug researching and syntheses of chiral drugs. The related study and production is on fast rise. New amoni acids and their derivates have always been the key point of chemists′research. This dissertation deals with the synthesis of some novel amoni acids derivates based on cheap and easy making materials.Using Ivdde as the terminal amino group protector for four amoni acids with different carbon chain length, which are Fmoc-Dap-OH, Fmoc-Dab-OH, Fmoc-Orn-O and Fmoc-Lys-OH, four derivates were obtained named as Fmoc-Dap(Ivdde)-OH, Fmoc-Dab(Ivdde)-OH, Fmoc-Orn(Ivdde)-OH and Fmoc-Lys(Ivdde)-OH respectively. The synthetic procedure of the four amoni acids in our work has been proved to be of feasible value and can be applied into large scale production.Our second part of work based on the fact that enantiopure non-proteinogenic amino acids play a major role in the synthesis of peptidomimetics like HIV protease inhibitors, thrombin inhibitors and inducers for the for-mation ofβ-turns to influuence protein folding. Especially 3,(4)-substituted prolines1 and (pyro)glutamates as building blocks in bioactive peptides can give additional information about receptor recognition1fand affinity. (S)-Pyroglutamic acid was transformed into the Cbz-protected 4-methyl-2,6,7-trioxabicyclo[2.2.2] octane (OBO) ester. This ortho ester functionality was employed as a bulky steering group for stereoselective introduction of alkyl and aryl groups via 1,4-cuprate addition to 3,4-unsaturated pyroglutamates. After deprotection and ring-opening, (2s,3s)-3-methyl-glutamic acid was obtained successfully in the current work.更多还原