Rapid and Controllable Hydrogen/Deuterium Exchange on Aromatic Rings of α‐Amino Acids and Peptides

Abstract

Novel hydrogen/deuterium exchange for aromatic α-amino acids and their corresponding peptides were performed through the use of deuterated trifluoromethanesulfonic acid (TfOD). Detailed analysis of the exchange revealed that equal hydrogen/deuterium exchange was observed for phenylalanine, and specific exchange at the ortho-positions of phenol for tyrosine was also detected. The stereochemistry of the aromatic α-amino acids was retained under the exchange conditions. The hydrogen/deuterium exchange properties for these aromatic α-amino acids are identical for peptides that contain several aromatic α-amino acids. The exchange proceeded significantly faster than previous methods. Detailed analysis of the exchange revealed that the method could be controlled by temperature, time, and the amount of reagent

Hydrogen/deuterium exchange of cross-linkable α-amino acid derivatives in deuterated triflic acid

“…These results indicate that the exchange rate for N-acetyl-protected aromatic α-amino acids is faster than that for unprotected compounds. Based on the above observations, N-Ac-L-DOPA (9), N-Ac-L-Phe(4-benzoyl) (10), and N-Ac-L-Phe(4-TFMD) (11) were subjected to H/D exchange in TfOD. For DOPA derivative 9, the N-protection did not cause improvement in H/D exchange drastically because unprotected 1 is a good substrate for our H/D exchange.…”

“…The exchange can be monitored regularly and controlled by adjusting the reaction temperature and reagent ratio. 10) We report in this paper the post-H/D exchange for cross-linkable aromatic α-amino acid derivatives with TfOD under mild conditions.…”

Trifluoromethanesulfonic Acid as Acylation Catalyst: Special Feature for C- and/or O-Acylation Reactions

“…Otherwise, non-deuterium incorporation at the α-proton of carbonyl indicates formation of either the acyl cabonium ion 116 or protonated carbonyl of mixed anhydride 117. TfOD catalysis of the direct C-acylation of toluene 118 and glutamic acid derivatives 66b has been previously established (Scheme 16) [74]. The deuterium incorporation was observed only on the aromatic protons (68%-75% deuterium incorporation) at a fine yield (94%) of the acylated product 119.…”

“…In the TfOD-catalyzed acylation of toluene 118 with glutamic acid derivatives 66b, the deuterium incorporation occurred only at aromatic protons, indicating the absence of α-proton deprotonation and that formation of ketene 115 formations was not possible. TfOD catalysis of the direct C-acylation of toluene 118 and glutamic acid derivatives 66b has been previously established (Scheme 16) [74]. The deuterium incorporation was observed only on the aromatic protons (68%-75% deuterium incorporation) at a fine yield (94%) of the acylated product 119.…”

“…A study that used a D2O/D2SO4 system found that conditions will lead to either partial or complete racemization of phenylalanine H/D exchange, which is indicated by the exchange of α-protons [79]. Deuterated TFA (TFA-d) is appropriate for slow H/D exchange [80], TfOD catalysis of the direct C-acylation of toluene 118 and glutamic acid derivatives 66b has been previously established (Scheme 16) [74]. The deuterium incorporation was observed only on the aromatic protons (68%-75% deuterium incorporation) at a fine yield (94%) of the acylated product 119.…”