Sorbents with immobilized glycopeptide antibiotics for separating optical isomers by high-performance liquid chromatography

Abstract

The increasing attention being paid by researchers to studies in the field of stereoselective synthesis and catalysis, as well as methods of chromatographic separation of chiral phases, observed over the last decade, is due to the requirements of the World Health Organization for the optical purity of drugs. The lack of universally applicable chiral phases for separating optical isomers prompts researchers to develop new sorbents. Immobilized macrocyclic glycopeptide antibiotics (including vancomycin, teichoplanin, ristocetin A, avoparcin, etc.) proved to serve as chiral phases for reliable HPLC separation of a wide range of drugs [1][2][3][4]. The high enantioselectivity of the sorbents belonging to this class is due to the presence of structurally diverse fragments capable of multiple-point interactions with the compounds to be separated (in both polar and nonpolar solvents). Immobilization of new antibiotics [5], chemical modifications of their structure [6], and refinement of immobilization techniques [7] offer additional possibilities for changing the enantioselectivity of sorbents belonging to this class.It was previously shown that eremomycin (a new antibiotic manufactured in Russia), in contrast to its closest structural analogue vancomycin, exhibits high enantioselectivity in separating isomers of α amino acids when immobilized on silica gel [8]. A method of its immobilization was developed that increased the selectivity of the separation, thus, rendering the sorbent superior to other chiral selectors in separating isomers of α amino acids [9].In this work, we sought to explore the capacity of the new eremomycin sorbent for separating enantiomers of other classes (profens) and study the effects of structural modification of eremomycin on its enantioselectivity, as compared to the known chiral selectors vancomycin and ristomycin. MATERIALS AND METHODSReagents. The antibiotics were immobilized using modified silica gels: Diaspher-110-Epoxy (particle size, 6 µ m; specific surface, 313 m 2 /g; pore diameter, 11 nm; carbon content, 5.2%) and Diasorb-130-Epoxy (particle size, 6 µ m; specific surface, 280 m 2 /g; pore diameter, 13 nm; carbon content, 4.8%) manufactured by BioChemMack ST Russia. The eluants were prepared using methanol, acetic acid, and triethylamine (Fluka, Switzerland). Eremomycin and ristomycin were synthesized using a pilot plant at the Hause Institute for New Antibiotics (Russia) [10,11]. Vancomycin was provided by the joint stock company Veropharm (Russia). The profens and amino acids were purchased from Sigma (United States).Obtaining eremosaminyl aglycon of eremomycin [4]. Eremomycin (3 g) was dissolved in 30 ml of dimethyl sulphoxide, and the solution was supplemented with 2 ml of 80% sulfuric acid, after which the mixture Kuznetsov a , P. N. Nesterenko a , G. G. Vasiyarov a , and S Abstract -Chiral sorbents for HPLC separation of optical isomers carrying glycopeptide antibiotics (eremomycin or its eremosaminyl aglycon, ristomycin, or vancomycin) fixed onto the surface of silica gel...

Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

“…For HPLC separation of the 4a/4b mixture, a hybrid sorbent (silica gel with immobilized eremomycin) was chosen. This chiral selector has been reported to possess good enantio-selectivity toward modified α- and β-amino acids and their derivatives [ 50 – 51 ]. The separation of the S - and R -monomers, 4a and 4b , was relatively efficient under the selected conditions ( Fig 2A ).…”

Chiral selectors in CE: Recent developments and applications

“…A new macrocyclic glycopeptide antibiotic, eremomycin, was recently added in the family of CSs, and it is a structural analog of vancomycin . Prokhorova et al.…”

“…A new macrocyclic glycopeptide antibiotic, eremomycin, was recently added in the family of CSs, and it is a structural analog of vancomycin [161]. Prokhorova et al [162] used eremomycin, for the first time, as a chiral additive in CE for the enantioseparation of profens.…”

Daptomycin: A Novel Macrocyclic Antibiotic as a Chiral Selector in an Organic Polymer Monolithic Capillary for the Enantioselective Analysis of a Set of Pharmaceuticals

“…Macrocyclic drugs, including ansamycins, glycopeptides, and the polypeptide antibiotic thiostrepton, have been widely utilized as chiral stationary phases (CSPs) for the enantioselective separations of racemates [1][2][3]. In particular, chiral selectors belonging to glycopeptides, such as vancomycin, colistin sulfate, norvancomycin, ristocetin A, teicoplanin, eremomycin, and others, have been successfully used in different chromatographic setups [1,4,5] to achieve the enantioselective resolution of racemic amino acid derivatives and profens [6][7][8][9][10].…”