COUPLING N-METHYLATED AMINO-ACIDS USING PYBROP AND PYCLOP HALOGENOPHOSPHONIUM SALTS - MECHANISM AND FIELDS OF APPLICATION

被引:146
作者
COSTE, J
FREROT, E
JOUIN, P
机构
[1] Laboratoire CNRS des Mécanismes Moléculaires des Communications Cellulaires, CCIPE, 34094 Montpellier Cedex 05, Rue de la Cardonille
关键词
D O I
10.1021/jo00088a027
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
PyBroP (1) and PyCloP (2), two halotripyrrolidinophosphonium hexafluorophosphates, are peptide-coupling reagents highly efficient for coupling N-methylated amino esters, in contrast with PyBOP (3), the hydroxybenzotriazolyl analogue. These halogenophosphonium salts 1 and 2 are convenient (one-pot reactions) stable solids soluble in conventional solvents. Use of them gave an excellent peptide yield with essentially no epimerization. Activation with these reagents probably involves the formation of an (acyloxy)phosphonium, as shown in the case of 2,4,6-trimethylbenzoic acid activation. In the case of reagents 1 and 2, oxazolone and/or a symmetrical anhydride were intermediates which were rapidly aminolyzed. In contrast, the benzotriazolyl ester intermediate which was formed with PyBOP (3) was poorly reactive with N-methylated amino esters. PyBroP (1) and PyCloP (2) were less efficient in the coupling of some Boc-amino acids because of N-carboxyanhydride formation; this was particularly the case when Boc-Val-OH or Boc-MeVal-OH was coupled with MeVal-OMe.
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页码:2437 / 2446
页数:10
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