A facile synthesis of cysteine-based diketopiperazine from thiol-protected precursor

Abstract

l-Cysteine is one of the most promising biomass-based building blocks with great potential applications. Herein, we report a versatile synthetic route to produce cysteine-based 2,5-diketopiperazine (DKP) with good yield from the thiol-ene click reaction of l-cysteine and commercially available acrylates, followed by dimerization of the amino acid intermediates. The achieved DKP diastereomers were successfully separated and fully characterized by spectroscopic methods. Moreover, the chiroptical property of DKP in the presence of various metal ions was investigated by circular dichroism spectroscopy. The potential application of the optically active cysteine-based DKP as a chiral probe for detection of silver ion in water has been demonstrated.

Stereochemical Effects on the Antimicrobial Properties of Tetrasubstituted 2,5-Diketopiperazines

“…(Figure ). This observed difference for H-2 is consistent with the cis versus trans relationship at the C α position. , …”

“…This observed difference for H-2 is consistent with the cis versus trans relationship at the C α position. 37,38 To further understand the importance of stereochemistry for the DKP bioactivity, in silico molecular dynamics and membrane insertion studies were performed. Solution dynamic modeling predicted that both DKPs 1 and 2 would have largely amphipathic structures in solution.…”

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

“…The C-C disconnection ( Scheme 1 , C) often involves enolate acylation, albeit radical routes were also described to attain the C-C cyclization [ 63 ]. Despite the various synthetic routes available, the search is still active in this area with new developments pertaining to CDP synthesis appearing also in the most recent literature [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

2,5-Diketopiperazines via Intramolecular N-Alkylation of Ugi Adducts: A Contribution to the Synthesis, Density Functional Theory Study, X-ray Characterization, and Potential Herbicide Application

“…A wide variety of 2,5-DKP has been isolated from plants, fungi, bacteria, and mammalian and marine organisms, and many of such compounds have shown promising and relevant biological properties. ,− Their ability to bind a wide variety of biological receptors has been attributed to their conformationally rigid backbone, capable of mimicking preferential peptide conformation, and to the increased stability of the 2,5-DKP core against proteolysis in comparison to acyclic dipeptides, which allows for such drug-like properties. Such biological properties have made 2,5-DKPs promising scaffolds for the development of novel therapeutic agents, leading to the emergence of different methods for obtaining synthetic 2,5-DKPs. − The progress on the synthetic strategies toward 2,5-DKP up to 2012 has been reviewed, but novel strategies have emerged . A classical methodology for the construction of the 2,5-DKP ring consists of the amidation reaction between an activated carboxyl group of an N -Boc-protected amino acid with the amine group of a C -protected amino acid (amino acid ester).…”