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题名	新方法制备2-氯三苯甲基氯树脂及其多肽固相合成应用
作者	李鹏
学位类别	硕士
答辩日期	2009-05-26
授予单位	中国科学院过程工程研究所
授予地点	过程工程研究所
导师	苏志国
关键词	2-氯三苯甲基氯 聚苯乙烯树脂 多肽固相合成
其他题名	Novel preparation of 2-chlorotritylchloride resin and its application in solid-phase peptide synthesis
学位专业	生物化工
中文摘要	在多肽固相合成领域，2-氯三苯甲基氯（2-chlorotritylchloride, 2-CTC）树脂因其反应条件温和、有效抑制副反应、产物纯度高等优点，被越来越多的应用于生物活性肽类的研究开发，特别是药用短肽的实际生产中。其优良的性能和广泛的用途决定了2-CTC树脂不再只是实验室常用的合成载体，将逐渐成为大批量使用的生产用载体树脂。然而目前已有的几种2-氯三苯甲基氯-聚苯乙烯(2-CTC-PS)树脂的制备方法均包括复杂的操作步骤且必须使用有机金属试剂，如由碘代苯聚合物和n-丁基锂衍生的锂-苯聚合物与苯甲酮反应生成三苯甲基聚合物；或由聚苯乙烯树脂和苯甲酰氯通过Friedel-Crafts酰化反应衍生成聚合物，再通过锂试剂转化为三苯甲基聚合物。因此复杂的反应操作条件、试剂成本及废料的处理可能会成为2-CTC树脂规模化生产中较难解决的问题。 为此，本研究采用较廉价的2-氯二苯甲酮作为原料，通过简便的氯化方法制得1-氯-2-二氯苯甲基苯(1-chloro-2-(dichloro(phenyl)methyl)benzene，DCPB)作为连接前体，再与聚苯乙烯进行Friedel-Crafts烷基化反应在树脂载体上得到三苯甲基醇结构，最后通过氯化反应得到2-CTC-PS树脂产品。该制备方法反应条件温和，处理过程简便且无需使用有机金属试剂。采用该方法制备的小粒径2-CTC-PS树脂 (1.5% DVB交联，粒径小于30μm) 溶胀性质优良，首位氨基酸上载水平达到1.4mmol/g，使用制备树脂合成的胸腺五肽(TP-5)收率为91%，纯度达到98.5%；合成的“困难序列”酰基载体蛋白65-74(ACP65-74)收率为72%，纯度达到76.5%。
英文摘要	2-Chlorotritylchloride (2-CTC) resin has been used more and more frequently in solid-phase peptide synthesis (SPPS). Due to its several advantages such as moderate reaction condition, efficient restraining of side reaction and high product purity, the use of 2-CTC resin has been expanded from laboratory to large-scale production of pharmaceutical peptides. However, the current methods for preparation of 2-CTC resins all involve complicated procedures using organometallic reagents. For instance, the lithlo-phenyl polymer derived from iodophenyl polymer and n-butyllithium reacted with benzophenone to give the tritylated polymer; or inversely, polymeric benzophenone derivatives were prepared from benzoyl chlorides via Friedel-Crafts acylation, and then converted to the trityl structure on the resin with lithium reagent. It is important to develop a novel process of 2-CTC synthesis to minimize costly reagents and disposal problems. In this paper, a new route was designed using a new reagent for the reaction. 1-Chloro-2-[dichloro(phenyl)methyl]benzene (DCPB) was the pseudo-activated linker, which can be easily derived from 2-chlorobenzophenone. DCPB conjugated to polystyrene by Friedel-Crafts acylation to obtain 2-chlorotritylalcohol (2-CTA) structure on the resin. After chlorination of the resultant 2-CTA resin with thionylchloride, 2-CTC resin was prepared. The new method has only three steps which could be processed under mild conditions without any organometallic reagents. The 2-CTC resin with small particle diameter prepared in this new simple method showed excellent swelling properties and its initial amino acid loading level was up to 1.4mmol/g. In solid-phase synthesis of peptide sequences, thymopentin (TP-5) were obtained in the yield of 91% and the purity of 98.5%. A difficulty sequence, fragment 65-74 of acyl carrier protein (ACP 65-74) were obtained in the yield of 72% and the purity of 76.5%.
语种	中文
公开日期	2013-09-16
页码	80
内容类型	学位论文
源URL	[http://ir.ipe.ac.cn/handle/122111/1289]
专题	过程工程研究所_研究所（批量导入）
推荐引用方式 GB/T 7714	李鹏. 新方法制备2-氯三苯甲基氯树脂及其多肽固相合成应用[D]. 过程工程研究所. 中国科学院过程工程研究所. 2009.

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