碳酸酯把手改构Wang树脂及其性能
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摘要
基于碳酸酯结构易于亲核脱除的原理,使用氯甲酸氯甲酯改构Wang树脂,并探究了改构树脂与首位氨基酸的缩合效率.实验结果表明,改构后的Wang树脂与20种Fmoc保护氨基酸均能达到70%以上的缩合效率;且对于带有较大侧链基团的Fmoc保护氨基酸,通过降低树脂取代度或延长反应时间可提高其连接率.为了验证改构后的碳酸酯型树脂在裂解时侧链未受到影响,设计合成了3种模型肽,并用温和裂解剂3-吡啶甲醛肟铯盐进行裂解.实验结果表明,利用改构树脂能得到侧链全保护的肽片段,可初步应用到长链困难肽的合成中.
Because of the carbonate structure is removed by nucleophilic agents easily,methyl chloroformate was used to modify Wang resin,and the condensation efficiency of modified Wang resin with the first amino acid was studied. The results showed the condensation efficiency of the modified resin to 20 kinds of Fmoc amino acids could run up to 70%. In order to increase the condensation efficiency of the modified resin with the Fmoc amino acids achieving larger side chain groups,the degree of resin substitution was reduced and the reaction time was prolonged. In order to prove the protected side chain group would not be damaged under cleavage conditions of the modified Wang resin,three model peptides were resigned and synthesized,and cleaved by 3-pyridinecarboxaldehyde sulfonium salt. The results showed that the peptides with side chain fully protected could be obtained by using the modified Wang resin,and could also be preliminary applied to the synthesis of long-chain peptides.
Because of the carbonate structure is removed by nucleophilic agents easily,methyl chloroformate was used to modify Wang resin,and the condensation efficiency of modified Wang resin with the first amino acid was studied. The results showed the condensation efficiency of the modified resin to 20 kinds of Fmoc amino acids could run up to 70%. In order to increase the condensation efficiency of the modified resin with the Fmoc amino acids achieving larger side chain groups,the degree of resin substitution was reduced and the reaction time was prolonged. In order to prove the protected side chain group would not be damaged under cleavage conditions of the modified Wang resin,three model peptides were resigned and synthesized,and cleaved by 3-pyridinecarboxaldehyde sulfonium salt. The results showed that the peptides with side chain fully protected could be obtained by using the modified Wang resin,and could also be preliminary applied to the synthesis of long-chain peptides.
引文
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[2] Nan Y. P.,Chemistry&Bioengineering,2005,22(6),34—36(南亚萍.化学与生物工程,2005,22(6),34—36)
[3] Tang H. K.,Studies on Solid-Phase Synthesis,Purification and Preparation of Peptide JFT,Northwest University,Xi’an,2007(唐宏琨.减肥多肽JFT的固相合成及纯化制备工艺研究.西安:西北大学,2007)
[4] Yang F. L.,Li H. S.,Wang J. L.,Shanghai Medical&Pharmaceutical Journal,2010,31(9),414—416(燕方龙,李洪森,王金龙.上海医药,2010,31(9),414—416)
[5] Han X.,Wang D. X.,Acta Pharmaceutica Sinica,2007,42(2),111—117(韩香,王德心.药学学报,2007,42(2),111—117)
[6] Huang B.,Henan Chemical Industry,2013,30(1),28—30(黄蓓.河南化工,2013,30(1),28—30)
[7] Behrendt R.,White P.,Offer J.,J. Pept. Sci.,2016,22(1),4—5
[8] Wang W. G.,Chen W. H.,Wen F.,Journal of Nanjing University of Technology,2007,29(1),12—15(卫国,陈伟华,闻峰.南京工业大学学报,2007,29(1),12—15)
[9] Chen Y. L.,Chemical Synthetic Research on Peptide Segments Ligation,Peptide Derivatives and Conjugate of Modifer-peptidederivative,Shandong University,Jinan,2009(陈艳丽.多肽片段连接、衍生物及偶合物的化学合成研究,济南:山东大学,2009)
[10] Fu Y. W.,Wu L.,Chemical Industry and Engineering,2010,27(4),92—97(符友伟,吴蕾.化学工业与工程,2010,27(4),92—97)
[11] Góngora B. M.,Tulla P. J.,ACS Combination Science,2013,15(5),217—228
[12] Subirós F. R.,Faham A.,Albericio F.,Biopolymers,2012,98(2),89—97
[13] Ieronymaki M.,Androutsou M.,Pantelia A.,Biopolymers,2015,104(5),506—514
[14] Han Y. B.,Li Y.,Yang G. Q.,Progress in Chemistry,2004,16(2),142—148(韩永滨,李嫕,杨国强.化学进展,2004,16(2),142—148)
[15] Albericio F.,Barany G.,Tetrahedron Letters,1991,32(8),1015—1018
[16] Wang D. X.,Solid-Phase Organic Synthesis:Principle and Application Guide,Chemical Industry Press,Beijing,2004,543(王德心.固相有机合成———原理及应用指南,北京:化学工业出版社,2004,543)
[17] Lou S. J.,Xiang H.,Huang H.,Ion Exchange and Adsorption,1999,15(1),15—22(娄素君,向新,黄海.离子交换与吸附,1999,15(1),15—22)
[18] Wu N.,Study on the Handle of Hydroquinones for Peptide Solid Phase Synthesis,The Chemical Defence Collage,Beijing,2010(吴宁.用于肽类固相合成的羟基酸酯类把手的研究,北京:防化学院,2010)
[19] Zong L.,Dong J. J.,Chen J.,Chem. J. Chinese Universities,2016,37(7),110—116(宗良,董俊军,陈静.高等学校化学学报,2016,37(7),110—116)
[20] Wang W. G.,Chen W. H.,Wen F.,Journal of Nanjing Tech University,2007,29(1),12—15(王卫国,陈伟华,闻峰.南京工业大学学报,2007,29(1),12—15)