Breipohl G, Knolle J, Stüber W
Research Laboratories of Hoechst AG, Frankfurt, Federal Republic of Germany.
Int J Pept Protein Res. 1989 Oct;34(4):262-7. doi: 10.1111/j.1399-3011.1989.tb01573.x.
The preparation and application of a new linker for the synthesis of peptide amides using a modified Fmoc-method is described. The new anchor group was developed based on our experience with 4,4'-dimethoxybenzhydryl (Mbh)-protecting group for amides. Lability towards acid treatment was increased dramatically and results in an easy cleavage procedure for the preparation of peptide amides. The synthesis of N-9-fluorenylmethoxycarbonyl- ([5-carboxylatoethyl-2.4-dimethoxyphenyl)- 4'-methoxyphenyl]-methylamin is reported in detail. This linker was coupled to a commercially available aminomethyl polystyrene resin. Peptide synthesis proceeded smoothly using HOOBt esters of Fmoc-amino acids. Release of the peptide amide and final cleavage of the side chain protecting groups was accomplished by treatment with trifluoroacetic acid-dichloromethane mixtures in the presence of scavengers. The synthesis of peptide amides such as LHRH and C-terminal hexapeptide of secretin are given as examples.
描述了一种使用改良的Fmoc方法合成肽酰胺的新型连接子的制备及其应用。新的锚定基团是基于我们在酰胺的4,4'-二甲氧基二苯甲基（Mbh）保护基团方面的经验开发的。对酸处理的不稳定性显著增加，从而形成了一种用于制备肽酰胺的简便裂解方法。详细报道了N-9-芴甲氧羰基-([5-羧基乙基-2,4-二甲氧基苯基)-4'-甲氧基苯基]-甲基胺的合成。该连接子与市售的氨甲基聚苯乙烯树脂偶联。使用Fmoc-氨基酸的HOOBt酯，肽合成顺利进行。通过在清除剂存在下用三氟乙酸-二氯甲烷混合物处理来实现肽酰胺的释放和侧链保护基团的最终裂解。以促黄体生成素释放激素（LHRH）和促胰液素C末端六肽等肽酰胺的合成为例。
