Ekaterina Todadze

Long-range intramolecular S -> N acyl migration: a study of the formation of native peptide analogues via 13-, 15-, and 16-membered cyclic transition states

The intramolecular long-range S → N acyl migration via 13-, 15-, and 16-membered cyclic transition states to form native tetra- and pentapeptide analogues was studied on S-acylcysteine peptides containing β- or γ-amino acids. The pH-dependency study of the acyl migration via a 15-membered cyclic transition state indicated that the reaction is favored at a pH range from 7.0 to 7.6. Experimental observations are supported by structural and computational investigations.

Microwave-assisted chemical ligation of S-acyl peptides containing non-terminal cysteine residues

An efficient approach for the synthesis of a series of S-acyl peptides containing internal cysteine residues has been developed and the chemical long-range ligation of these S-acyl peptides via 5-, 8-, 11- and 14-membered cyclic transition states has been investigated. Our results include the first examples of successful isopeptide ligations starting from S-acyl peptides containing non-terminal cysteine residues and indicate that the cyclic transition states studied in this present paper are decreasingly favored in the order of their sizes 5≫14>11≫8.

A new benzotriazole-mediated stereoflexible gateway to hetero-2,5-diketopiperazines

Open chain Cbz-L-aa(1)-L-Pro-Bt (Bt=benzotriazole) sequences were converted into either the corresponding trans- or cis-fused 2,5-diketopiperazines (DKPs) depending on the reaction conditions. Thermodynamic tandem cyclization/epimerization afforded selectively the corresponding trans-DKPs (69-75%). Complementarily, tandem deprotection/cyclization led to the cis-DKPs (65-72%). A representative set of proline-containing cis- and trans-DKPs has been prepared. A mechanistic investigation, based on chiral HPLC, kinetics, and computational studies enabled a rationalization of the results.

Selective Peptide Chain Extension at the N‐terminus of Aspartic and Glutamic Acids Utilizing 1‐(N‐protected‐α‐aminoacyl)benzotriazoles

Diverse N‐protected di‐(3a–d, 3a + a′, 5a–d, 5d + d′, and 7a–g) and tripeptides (10a–h) were synthesized under mild reaction conditions in good yields (65–97%) by acylation with 1‐(N‐protected‐α‐aminoacyl)benzotriazoles of the amino groups of free aspartic and glutamic acids. Complete retention of chirality was demonstrated by parallel experiments involving d‐Ala, l‐Ala, and dl‐Ala for the preparation of dipeptides and tripeptides, and supported by NMR and HPLC analyses.

Efficient microwave-assisted synthesis of aminoxy acid conjugates

A representative set of Cbz-protected (α-aminoxyacyl)benzotriazoles was utilized as versatile building blocks for the efficient and convenient synthesis of novel α-aminoxy acid conjugates. Convenient protocols were developed for their regioselective preparation with sterically hindered nucleophiles such as sugars, terpenes, steroids and nucleosides.

Relative stabilities of 1- and 2-substituted 1,2,3-triazoles

N-(α-Aminoalkyl)-1,2,3-triazoles are potentially tautomeric between the 1- and 2-substituted forms. They exist in solution predominantly as 2-isomers as shown by 1 H and 13 C NMR; electron attracting substituents on the amino nitrogen increase the proportion of the 1-isomer in the equilibrium mixture.

Labeling of nucleosides with fluorescent 6-chloro-2,3-napthalimide

The synthesis and fluorescence properties of new highly fluorescent nucleosides are reported. 6-Chloro-2,3-napthalimides activated with benzotriazole and chlorine label nucleosides quickly and efficiently in yields of 70-82%: the products exhibit quantum efficiencies of 10-94% in solvents of diverse polarity.