Synthesis of Tetrapeptides Containing Dehydroalanine, Dehydrophenylalanine and Oxazole as Building Blocks for Construction of Foldamers and Bioinspired Catalysts

Abstract

The incorporation of dehydroamino acid or fragments of oxazole into peptide chain is accompanied by a distorted three-dimensional structure and additionally enables the introduction of non-typical side-chain substituents. Thus, such compounds could be building blocks for obtaining novel foldamers and/or artificial enzymes (artzymes). In this paper, effective synthetic procedures leading to such building blocks—tetrapeptides containing glycyldehydroalanine, glycyldehydrophenylalanine, and glycyloxazole subunits—are described. Peptides containing serine were used as substrates for their conversion into peptides containing dehydroalanine and aminomethyloxazole-4-carboxylic acid while considering possible requirements for the introduction of these fragments into long-chain peptides at the last steps of synthesis.

Insight into the Structure of Victorin, the Host-Selective Toxin from the Oat Pathogen Cochliobolus victoriae. Studies of the Unique Dehydroamino Acid β-Chlorodehydroalanine

“…For the purpose of the synthesis of the model compounds 3 and 4 , dipeptide Boc-Gly-ΔAla-OMe and tripeptide Cbz-Gly-ΔAla-Gly-OMe were obtained using a multistep procedure including preparation of an N -protected Gly-ΔAla fragment followed by its esterification reaction with a cesium salt and methyl iodide or coupling with a glycine methyl ester using a mixed anhydride protocol, , respectively.…”

“…The Boc-Ser-NHMe was prepared (please, see Supporting Information). Dehydration using a one pot procedure with methanesulfonyl chloride/DBU was performed, 48 but a complex reaction mixture was obtained. Thus, the preparation of a methanesulfonyl serine derivative and an elimination reaction were conducted in separate steps (Figure 6b).…”

“…In the next step, Ac-ΔAla-OH was converted into methylamide derivative Ac-ΔAla-NHMe using a mixed anhydride method with isobutyl chloroformate (Figure 6a), according to the known procedure. 45 For the purpose of the synthesis of the model compounds 3 and 4, dipeptide Boc-Gly-ΔAla-OMe and tripeptide Cbz-Gly-ΔAla-Gly-OMe were obtained using a multistep procedure including preparation of an N-protected Gly-ΔAla fragment 46 followed by its esterification reaction with a cesium salt and methyl iodide 47 or coupling with a glycine methyl ester using a mixed anhydride protocol, 45,48 respectively.…”

Imidazole-amino acids. Conformational switch under tautomer and pH change

“…On the other hand, azole in the side chain can be used as building blocks for the construction of artificial metalloenzymes (Lenartowicz et al 2021 ). Azole rings can be also used as trans replacement agents (Kaczmarek et al 2021 ; Lenartowicz et al 2022 ). Our previous studies show that the amino acid residues containing azole rings in the main chain possess unusual conformational properties (Siodłak et al 2014b ; Staś et al 2026a , 2016b , 2021 ).…”