Use of onium salt-based coupling reagents in peptide synthesis

被引:224
作者
Albericio, F [1 ]
Bofill, JM
El-Faham, A
Kates, SA
机构
[1] Univ Barcelona, Dept Organ Chem, E-08028 Barcelona, Spain
[2] Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA
[3] PerSept Biosyst Inc, Framingham, MA 01701 USA
关键词
D O I
10.1021/jo980807y
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Peptide coupling methods derived from onium salts based on 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) are becoming incorporated in synthetic strategies more frequently than the classical carbodiimide methods. We have correlated the reactivity of various onium salts derived from HOXt (X = A, B), with the structure of the reagents in question. Thus, we confirmed that the aza derivatives are more reactive than the parent benzotriazole derivatives in both activation and coupling. In addition, the activation step is determined by the structure of the carbon skeleton. Thus, pyrrolidino derivatives appear to be reagents of choice relative to the piperidino analogues or those derived from trialkylamines. Furthermore although phosphonium salts are slightly less reactive than the corresponding aminium/uronium salts, the former should be used for the activation of hindered species, since the latter may lead to the formation of guanidino derivatives.
引用
收藏
页码:9678 / 9683
页数:6
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