Premium
Mechanistic Insight into the Lability of the Benzyloxycarbonyl (Z) Group in N ‐Protected Peptides under Mild Basic Conditions
Author(s) -
TenaSolsona Marta,
AnguloPachón César A.,
Escuder Beatriu,
Miravet Juan F.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201400154
Subject(s) - chemistry , lability , vicinal , moiety , tripeptide , carboxylate , nucleophile , amide , intramolecular force , stereochemistry , hydroxide , group (periodic table) , medicinal chemistry , protecting group , leaving group , aryne , tetrahedral carbonyl addition compound , peptide , organic chemistry , catalysis , biochemistry , alkyl
An unexpected lability of the benzyloxycarbonyl (Z) protecting group under mild basic conditions at room temperature is explained by a mechanism based on anchimeric assistance. It is found that the vicinal amide group stabilises the tetrahedral intermediate formed after nucleophilic addition of hydroxide to the carbonyl of the Z group. This effect operates in N ‐protected tripeptides and tetrapeptides but Z‐protected dipeptides are stable under the same conditions due to blockage of the vicinal amide NH by intramolecular H‐bonding with the terminal carboxylate moiety.