Serendipitous Discovery of Peptide Dialkyl Peroxides

Abstract

Dedicated to Professor Dieter Seebach on the occasion of his 65th birthdayIn an attempt to synthesize a homologous series of peptide peresters, we investigated the reaction of the oxazol-5(4H)-ones of Pht-(Aib) n -OH (n 2 ± 8) and tert-butyl hydroperoxide in the presence of 4-(dimethylamino)pyridine. Unexpectedly, the major product isolated in each case proved to be the peptide dialkyl peroxide. This novel class of peptide derivatives was characterized by FT-IR, 1 H-NMR, MS, cyclic voltammetry, and X-ray diffraction. On the basis of the experimental data, a plausible mechanism is proposed for this reaction.Introduction. ± In the last few years, the study of intramolecular electron-transfer (ET) reactions in donor-spacer-acceptor (D-spacer-A) molecules has provided relevant information on how electrons are transferred through bonds and through space (solvent). We have recently investigated intramolecular ET reactions in systems in which A undergoes reductive cleavage of a s-bond (dissociative electron transfer, DET). More specifically, as illustrated in Scheme 1, the phthalimido (Pht) moiety of Aib (a-aminoisobutyric acid), which is easily reduced to its radical anion, was selected as the donor D. In this system, the acceptor A is the Aib-O-O t Bu perester function, a well-characterized dissociative-type acceptor [1]. Interestingly, we found in our electrochemical study that the DET rate of Pht-Aib-O-O t Bu is several orders of magnitude lower than the adiabatic limit.

Insights into the Distance Dependence of Electron Transfer through Conformationally Constrained Peptides

“…The synthesis of the D‐B‐A systems 1 0 – 5 (Scheme ) was described previously . The insertion of a perester acceptor at the carboxylic side of the oligo‐Aib peptide requires using a β ‐amino acid, otherwise the resulting perester is unstable and undergoes spontaneous decarbonylation to form a dialkylperoxide . As the insertion of two carbon atoms between the carbonyl group and the nitrogen atom could have imparted undesired flexibility to the backbone, we decided to use the trans ‐2‐aminocyclohexane carboxylic acid.…”

Cyclic α-amino acids as precursors for synthesis of 2-amino-3-hetarylpyrrolin-4-ones and their spiro derivatives

“…The cyclic a-amino acids were shown to behave like disubstituted a-amino acids, thus presumably yielding corresponding spiro-aminopyrrolinones in similar reaction sequences. Therefore, a-aminoisobutanoic acid (1a), 1-aminocyclopropane (1b), 1-aminocyclopentane (1c), and 1-aminocyclohexanecarboxylic acids (1d) were converted into the corresponding phthalimidoacid chlorides 3a [35][36][37], 3b [38], 3c [39], and 3d [40,41].…”

Crystal‐state 3D‐structural characterization of novel, Aib‐based, turn and helical peptides

“…Its sequence is based on an α-amino acid followed by a β-amino acid. The Aib ψ 1 torsion angle is indicative of the onset of a helical conformation for this 'imide-type' residue [25,36]. The β-amino acid is partially folded, with the 'φ 2 ', δ (around the central C2B1-C2A bond), and 'ψ 2 ' torsion angles 144.6(2)°, −58.0(2)°, and −25.7(2)°, respectively [50].…”

“…All compounds were also characterized by 1 H-NMR spectrometry (data not shown). The syntheses and characterizations of peptides 2 II [25], 2 III [26], and 7 [25] have already been reported.…”