Synthesis of orthogonally protected azahistidine: application to the synthesis of a GHK analogue

Abstract

The synthesis of various orthogonally protected azahistidine derivatives are obtained via 1,3-dipolar cycloaddition reactions. The newly obtained amino-acids can be selectively deprotected either at the side chain or at the N-terminus of the amino acid and should thus allow the use of these derivatives in (solid phase) peptide synthesis.

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

“…Synthesis of 1,5-triazole-containing Gly-His-Lys analog 57 125 Interesting stable phosphohistidine (pHis) mimetics and phosphoryltriazolylalanines (pTza) have been developed by Kee et al 129 A cycloaddition of diethyl ethynylphosphonate with protected azidoalanine under both CuAAC and RuAAC conditions gave the desired pTza derivatives 58 and 59 in 72% and 68% yield, respectively (Scheme 29). According to molecular modeling, these compounds display favorable pHis-mimetic properties in terms of geometry and electronics.…”

Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control

“…The preparation of aza-histidine (Figure 10) has been already described [82] and the synthetic routes published to date to obtain the fully deprotected amino acid are usually rather long (seven steps) [83]. …”

“…[82] described the click chemistry based access to fully protected aza-histidine, suitable for solid phase peptide synthesis (Scheme 29). …”

Extensive Structure–Activity Relationship Study of Albicidin's C‐Terminal Dipeptidic p‐Aminobenzoic Acid Moiety

“…Possibly,t he deleterious effect caused by the Table 1. Assignment of the residuesf or albicidin analogues with sequential deletion of the substituents of the C-terminal dipeptidic moiety (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), sequential replacement of the methoxy groups with ethoxyg roups (18)(19)(20), sequentialr eplacement of the phenolic core structure with pyridines (21-23), andw ith replacement of the carboxylic acid groupw ith a sulfonic acid group( 24). All derivatives contain azahistidine as building block C. O ne could conclude that the hydroxy group in building block Fi s imperative, but ad irect comparison of 22,f or example, with the trisubstituted ands till active analogue 6,n egates that assumption and makes adversee lectronic effects and H-bonding interactions between the nitrogen atom of the pyridine and the adjacent carboxylg roup more likely.…”