Chiral separation of underivatized amino acids in supercritical fluid chromatography with chiral crown ether derived column

Miller, Larry; Yue, Lei

doi:10.1002/chir.23204

Cited by 25 publications

(16 citation statements)

References 23 publications

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“…These limitations mentioned above provide opportunities for further extensive studies. Additionally, there are also recent publications on the direct resolution of amino acids using SFC and HPLC. , These approaches may be useful for any future work. However, such studies are beyond the scope of the present study.…”

Section: Resultsmentioning

confidence: 99%

Chiral Chromatographic Isolation on Milligram Scale of the Human African Trypanosomiasis Treatment d- and l-Eflornithine

et al. 2020

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Eflornithine is a recommended treatment against the otherwise fatal parasitic disease late stage human African trypanosomiasis (HAT), also known as Gambian sleeping sickness. It is administered repeatedly as a racemic mixture intravenously (IV) together with oral nifurtimox. Racemic eflornithine has been investigated in clinical trials for oral dosing. However, due to low systemic exposures at a maximum tolerated oral dose, the drug is continued to be administered IV. The eflornithine enantiomers, d - and l -eflornithine, have different affinities to the target enzyme ornithine decarboxylase, suggesting that the pharmacodynamics of the enantiomers may differ. The aim of this study was to develop a method for isolation of d - and l -eflornithine from a racemic mixture. Several chiral stationary phases (CSPs) were evaluated for enantioselectivity using supercritical fluid chromatography (SFC) or high-performance liquid chromatography (HPLC). None of the tested CSPs rendered separation of the enantiomers in SFC mode. Separation of the enantiomers with SFC on the CSP Chiralpak IG was only achieved on an analytical scale after derivatization with ortho -phthalaldehyde (OPA). This was the first reported enantioselective SFC method for an eflornithine derivate. However, due to poor stability, the eflornithine-OPA derivates degraded and no chemically pure enantiomers were obtained. The CSP that showed enantioselectivity in HPLC mode was Chirobiotic R, which resulted in a successful isolation on a semipreparative milligram scale. The isolated eflornithine enantiomers will be tested in nonclinical in vitro and in vivo studies to support and assess the feasibility of a future clinical program with an oral HAT treatment.

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Section: Resultsmentioning

confidence: 99%

Chiral Chromatographic Isolation on Milligram Scale of the Human African Trypanosomiasis Treatment d- and l-Eflornithine

et al. 2020

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“…As an efficient, fast analytical technique, supercritical fluid chromatography (SFC) has been widespread in chiral chromatography, and it was successfully applied in the crown ether-based HPLC-MS separation of underivatized α-amino acids enantiomers [ 40 ]. All 18 selected amino acid racemates, except histidine, were separated within 3 min, and the obtained mean R S value was higher than 5.…”

Section: Recent Applications Of Crown Ether-based Cspsmentioning

confidence: 99%

Liquid Chromatographic Enantioseparations Utilizing Chiral Stationary Phases Based on Crown Ethers and Cyclofructans

et al. 2021

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Natural compounds can exist in different forms, where molecules possessing chirality play an essential role in living organisms. Currently, one of the most important tasks of modern analytical chemistry is the enantioseparation of chiral compounds, in particular, the enantiomers of compounds having biological and/or pharmaceutical activity. Whether the task is to analyze environmental or food samples or to develop an assay for drug control, well-reproducible, highly sensitive, stereoselective, and robust methods are required. High-performance liquid chromatography best meets these conditions. Nevertheless, in many cases, gas chromatography, supercritical fluid chromatography, or capillary electrophoresis can also offer a suitable solution. Amino acids, proteins, cyclodextrins, derivatized polysaccharides, macrocyclic glycopeptides, and ion exchangers can serve as efficient selectors in liquid chromatography, and they are quite frequently applied and reviewed. Crown ethers and cyclofructans possessing similar structural characteristics and selectivity in the enantiodiscrimination of different amine compounds are discussed less frequently. This review collects information on enantioseparations achieved recently with the use of chiral stationary phases based on crown ethers or cyclofructans, focusing on liquid chromatographic applications.

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“…This method of analysis makes it possible to quickly separate the pure standards of DL-amino acids. However, it can be improved to separate a complex mixture of all of them [105].…”

Section: Crown Ether-based Chiral Stationary Phasesmentioning

confidence: 99%

Recent Advances in Chiral Analysis of Proteins and Peptides

Morvan

Mikšı́k

2021

Separations

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Like many biological compounds, proteins are found primarily in their homochiral form. However, homochirality is not guaranteed throughout life. Determining their chiral proteinogenic sequence is a complex analytical challenge. This is because certain D-amino acids contained in proteins play a role in human health and disease. This is the case, for example, with D-Asp in elastin, β-amyloid and α-crystallin which, respectively, have an action on arteriosclerosis, Alzheimer's disease and cataracts. Sequence-dependent and sequence-independent are the two strategies for detecting the presence and position of D-amino acids in proteins. These methods rely on enzymatic digestion by a site-specific enzyme and acid hydrolysis in a deuterium or tritium environment to limit the natural racemization of amino acids. In this review, chromatographic and electrophoretic techniques, such as LC, SFC, GC and CE, will be recently developed (2018–2020) for the enantioseparation of amino acids and peptides. For future work, the discovery and development of new chiral stationary phases and derivatization reagents could increase the resolution of chiral separations.

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Chiral separation of underivatized amino acids in supercritical fluid chromatography with chiral crown ether derived column

Cited by 25 publications

References 23 publications

Chiral Chromatographic Isolation on Milligram Scale of the Human African Trypanosomiasis Treatment d- and l-Eflornithine

Chiral Chromatographic Isolation on Milligram Scale of the Human African Trypanosomiasis Treatment d- and l-Eflornithine

Liquid Chromatographic Enantioseparations Utilizing Chiral Stationary Phases Based on Crown Ethers and Cyclofructans

Recent Advances in Chiral Analysis of Proteins and Peptides

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