Application of the Suzuki‐Miyaura cross‐coupling reaction for the modification of phenylalanine peptides

Abstract

We have demonstrated an exceptionally simple and a useful methodology for modification of unusual phenylalanine peptides by adapting the building block approach using the Suzuki-Miyaura cross-coupling reaction as a key step. This strategy gave a good overall yield of various modified tri- and pentapeptides that may be useful to prepare various biologically active peptides in a short period of time.

Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1

“…The required aniline precursors were either purchased or, in the case of the amides, prepared via EDCI mediated coupling of amines with the appropriate benzoic acid derivatives (Scheme 1b). 11 This product was then coupled with methyl 2-mercaptobenzoate and subjected to the cyclization conditions (Scheme 1a). This synthetic methodology allowed for preparation of the benzoisothiazolone derivatives shown in Tables 1 and 2.…”

Post-assembly Peptide Modifications by Chemical Methods

“…Recently, Kotha and Lahiri reported modification of the phenylalanine peptides by utilizing the Suzuki crosscoupling reaction with the 4-iodo-L-phenylalanine-based peptides [15]. Various tri-and pentapeptides (e.g., 12) were prepared by the standard water-soluble carbodiimidemediated peptide coupling strategy.…”

Synthesis ofβ3-Homophenylalanine-Derived Amino Acids and Peptides bySuzuki Coupling in Solution and on Solid Support

“…Whereas short a-peptides [5] or even a-proteins [9] bearing the above mentioned (4-aryl) phenylalanine precursors have been modified by Suzuki-Miyaura cross-coupling, no such operation is known for b-or mixed a,b-peptides. While a-peptides are rapidly degraded in vivo and in vitro by a multitude of peptidases, substrates with incorporated homologated a-amino acids (i.e., b-amino acids) exhibit a superior stability profile [10].…”

“…-The Suzuki-Miyaura cross-coupling reaction is a powerful synthetic tool for C,C-coupling reactions of borono derivatives with aryl or vinyl halides or triflates 5 ), as the reaction is unaffected by the presence of H 2 O, tolerates a broad range of functional groups, proceeds regio-and stereoselectively in good yields, and nontoxic inorganic side-products are easily removed. The reaction has been used with (4-borono)- [2], (4-bromo)- [3], and (4-iodo)phenylalanine [4] [5], serine-derived alkylboronic acids [6], and tyrosine triflates [3] [7] for the preparation of phenylalanine derivatives, which are modified in the 4-aryl position. These unnatural amino acids have been incorporated into small peptides to increase both their pharmacological potential and metabolic stability [8].…”