Augustyns K, Kraas W, Jung G
Institute of Organic Chemistry, University of Tübingen, Germany.
J Pept Res. 1998 Feb;51(2):127-33. doi: 10.1111/j.1399-3011.1998.tb00630.x.
An investigation of the stability of the Dde protecting group for amines, used in solid-phase peptide synthesis, shows that an unprotected epsilon-NH2 group of lysine can acquire the Dde protection from another epsilon-NH2 group or from an alpha-NH2 group. An unprotected alpha-NH2, however, cannot remove Dde from an epsilon-NH2 function. This migration takes place during Fmoc removal from the epsilon-NH2 with piperidine and/or during the subsequent washing steps. The Dde migration is also possible in neat dimethylformamide by a direct nucleophilic attack of the free epsilon-NH2 group. Addition of piperidine to the reaction medium accelerates the side reaction, probably because of the formation of an unstable piperidine-Dde adduct. Dde migration can be prevented if the 9-fluorenylmethyloxycarbonyl is cleaved with 1,8-diazabicyclo[5.4.0]undec-7-ene for a short reaction time (2%, 3 x 3 min). Finally, this rearrangement is shown to occur both as an intra- and intermolecular reaction between peptides on the same resin bead.
对用于固相肽合成的胺类的Dde保护基团稳定性的研究表明，赖氨酸的未保护ε-NH₂基团可从另一个ε-NH₂基团或α-NH₂基团获得Dde保护。然而，未保护的α-NH₂不能从ε-NH₂官能团上去除Dde。这种迁移发生在使用哌啶从ε-NH₂上去除Fmoc的过程中和/或随后的洗涤步骤中。通过游离ε-NH₂基团的直接亲核攻击，在纯二甲基甲酰胺中Dde迁移也是可能的。向反应介质中加入哌啶会加速副反应，这可能是由于形成了不稳定的哌啶-Dde加合物。如果用1,8-二氮杂双环[5.4.0]十一碳-7-烯在短反应时间（2%，3×3分钟）内裂解9-芴基甲氧基羰基，则可以防止Dde迁移。最后，这种重排被证明是在同一树脂珠上的肽之间作为分子内和分子间反应发生的。
