Synthesis of Nα-Z, Nβ-Fmoc or Boc protected α-hydrazinoacids and study of the coupling reaction in solution of Nα-Z-α-hydrazinoesters

Synthesis of hybrid hydrazino peptides: protected vs unprotected chiral α-hydrazino acids

“…Obtained results pointed to numerous obstacles associated with the usage of N α -benzyl hydrazino acids, starting from their incorporation into peptide chain to deprotection of the benzyl group. There are examples where coupling of N α -protected hydrazino derivatives to the activated amino acids, during solution and solid-phase synthesis was less effective (Bouillon et al 2007a , b ). Here we encountered problems with coupling to the activated N α -protected hydrazino acids and found that the conformational preferences of the nucleophile highly influence the outcome of the coupling reaction.…”

Peptidomimetics via modifications of amino acids and peptide bonds

“…224,231 The Mitsunobu protocol has been applied to the synthesis of chiral a-hydrazinoacid derivatives with high optical purity from a-hydroxyesters 54 (Scheme 12). [232][233][234] Free hydrazino acid derivatives 62 were prepared through the deprotection of the phthalimide group 60, and were then converted to N b -Fmoc-or N b -Boc-N a -(Cbz)-hydrazinoacid derivatives 63, which were more convenient for SPPS. 234 Baudy-Floc'h and co-workers reported a convenient method for the preparation of N b -Fmoc-substituted aza-b 3 -amino acids 66 by direct reductive amination of glyoxylic acid-N b -Fmoc-hydrazones (Scheme 13).…”

“…[232][233][234] Free hydrazino acid derivatives 62 were prepared through the deprotection of the phthalimide group 60, and were then converted to N b -Fmoc-or N b -Boc-N a -(Cbz)-hydrazinoacid derivatives 63, which were more convenient for SPPS. 234 Baudy-Floc'h and co-workers reported a convenient method for the preparation of N b -Fmoc-substituted aza-b 3 -amino acids 66 by direct reductive amination of glyoxylic acid-N b -Fmoc-hydrazones (Scheme 13). 227,228,235 In a similar approach, Burk et al achieved the enantioselective preparation of N-acylhydrazoacids by DuPHOS-Rh-catalyzed asymmetric hydrogenation of N-acylhydrazones derived from a-ketoesters.…”

“…Typically, natural peptide coupling systems are suitable for hydrazinoacid couplings. The proven methods for the hydrazide linkage include the use of coupling reagents such as DCC/DMAP, 252,253 EDCI/HOBt, 224 DIC, 229 DIC/HOBt, 227 HATU/NMM, 231 HBTU/HOBt/DIEA, 229 BOP/DIEA, 246 activated esters (OSu), 218,229,246,254 mixed anhydrides, 218 acid chlorides 254 fluorides 234,255 and N-(acyl)benzotriazoles. 230 In fact, the critical factor in obtaining hydrazino compounds is regioselectivity.…”

Pseudopeptide Synthesis via Fmoc Solid-Phase Synthetic Methodology

“…strategies were employed for the solid-phase synthesis of PFVh(Z)AL and PFh(Z)AVL as model hydrazinopeptides: a step-by-step synthesis, consisting of the coupling of N ,Northogonally protected hydrazinoacid 18, (Fig. N -Fmoc-N -Z-hydrazino acids 18 and building block 19 were prepared over six steps starting from commercially available -amino acids [109]. 11B).…”