Resolution of Chiral Drugs

You, Qidong

doi:10.1002/9781118075647.ch4

Cited by 6 publications

(5 citation statements)

References 95 publications

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“…Due to its easy availability, 1‐phenylamine is one of the widely used amines applied for resolving racemic mixtures of chiral acids into enantiomers. It has been used, for example, to obtain insect pheromones, as well as some drug substances in enantiomerically pure form. In the present study, we propose a method for resolving racemic mixtures of both endo ‐ and exo ‐monoesters of trans ‐norborn‐5‐ene‐2,3‐dicarboxylic acid in the form of their salts with ( R )‐ and ( S )‐1‐phenylethylamine ( (R)-1 and (S)-1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Preparation of optically pure substances by resolving racemates combined with readily available chiral compounds using repeated crystallization is still a procedure widely used in practice, since it ensures high purity of the products and good reproducibility of results . Several examples of resolving racemic trans ‐norborn‐5‐ene‐2,3‐dicarboxylic acid by repeated crystallization with chiral amines have been described, but no similar examples pertaining to its monoesters were reported.…”

Section: Introductionmentioning

confidence: 99%

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A Simple Method for Resolution ofEndo‐/Exo‐Monoesters ofTrans‐Norborn‐5‐Ene‐2,3‐Dicarboxylic Acids Into Their Enantiomers

Kovalenko

Kozyrkov

2014

Chirality

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Separation of optical isomers obtainable from trans-norborn-5-ene-2,3-dicarboxylic acid methyl and tert-butyl monoesters was performed by crystallization of the respective salts prepared with (R)- and (S)-1-phenylethylamine. Starting from racemic endo-monomethyl ester of trans-norborn-5-ene-2,3-dicarboxylic acid, prepared by partial hydrolysis of the cyclopentadiene-dimethyl fumarate adduct, the corresponding (2R,3R)-endo-monoester was isolated in 97% enantiomeric excess (ee) yield after seven repeated crystallizations from tetrachloromethane. Starting from exo-mono-tert-butyl ester of the same acid, prepared by alcoholysis of the cyclopentadiene-maleic anhydride adduct followed by isomerization, (2R,3R)-exo-monoester was isolated in >98% ee yield after four repeated crystallizations from ethanol. Crystallization of the acids from the mother liquor containing (S)-1-phenylethylamine yielded products with inverse stereochemical configuration.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Simple Method for Resolution ofEndo‐/Exo‐Monoesters ofTrans‐Norborn‐5‐Ene‐2,3‐Dicarboxylic Acids Into Their Enantiomers

Kovalenko

Kozyrkov

2014

Chirality

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“…Drug companies develop ways to obtain one enantiomer and produce a medication using only that enantiomer. Three strategies can be applied to obtain single pure isomers: (i) extraction from plants and animal materials (ii) enantio-selective asymmetric synthesis so that only one isomer is formed in the first place [40] or (iii) making a racemate and finding a method for separating the enantiomers (chiral resolution) [41][42][43]. Among the variety of enantioseparation methods, classical resolution [44], Simulated Moving Bed technology [45], chiral chromatography and crystallization are the most dominant methods for the recovery of pure enantiomers [46,47].…”

Section: B Enantiopure Drugs Preparationmentioning

confidence: 99%

Exploiting the Power of Stereochemistry in Drugs: An Overview of Racemic and Enantiopure Drugs

Sekhon¹

2013

J. Mod. Med. Chem.

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Stereochemistry is one of the essential dimensions in pharmacology as it dictates how enantiomers interact with biological systems. Chirality is very important in drug design. Enantiomers of the same chiral drug can have different pharmacodynamic and/or pharmacokinetic properties. In this context, replacing some existing racemates with single isomers has resulted in improved safety and/or efficacy profile of various racemates. Single enantiomer drug use can potentially lead to simpler and more selective pharmacologic profiles, improved therapeutic indices, simpler pharmacokinetics due to different rates of metabolism of the different enantiomers, decreased drug interactions, and drug companies are increasingly using chiral switching as a marketing strategy. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. However, unpredicted toxicity has been reported in some chiral switching cases which has resulted the withdrawal of the enantiomer from the market or a halt in its development. In view of above, before switching to single enantiomer drugs, prescribers should look for evidence from well-conducted clinical trials to prove that the chiral switch is cost-effective and improves the outcomes for patients rather than patents. The U.S. Food and Drug Administration (FDA) have allowed single enantiomers of generic drugs to be patented and marketed under different name. FDA regulations require that all chiral bioactive drug molecules must be isolated and tested for the efficacy and safety, and have to be as pure as possible containing a single pure enantiomer.

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“…XUE 1,* , Y.N. JIAO 2 and H. LI 2 high efficiency of separations, possibility to use new and inexpensive selectors, easy and fast method for development.…”

Section: Capillary Electrophoresis Separation Of the Six Pairs Of Chiral Pharmaceuticals Enantiomersmentioning

confidence: 99%

“…To improve drug activities and reduce side-effects, it is necessary to develop chiral separation research method of drug enantiomers for drug production and quality control. Therefore, chiral drugs separation and determination in pharmaceutical analysis will provide powerful means for pharmacology and toxicology research 1,2 . Among the chromatographic methods so far developed, high-performance liquid chromatography (HPLC) methods are widely employed for the assays of drug isomers in pharmaceutical preparations and biological fluids 3 , despite expensive commercial chiral columns [4][5][6][7] and low efficiency in the chiral stationary phases in the chiral chromatographic separation process during which most components need to be operated cumbersomely for pre-column derivatization and the objectivity of the results could be disturbed by artificial errors in improper intermediate process.…”

Section: Introductionmentioning

confidence: 99%

Capillary Electrophoresis Separation of the Six Pairs of Chiral Pharmaceuticals Enantiomers

Xue¹,

Jiao²,

Li³

2013

Asian J. Chem.

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Under the given voltage, temperature, wavelength, electrolyte concentration and pH value, the capillary electrophoresis was used in this study to separate six pairs of enantiomers (3-quinine alcohol, tamsulosin, etc.) simultaneously, three types of cyclodextrin being the chiral separation selectors. In order to increase the separation capabilities, the electrolyte was modified by polyethylene glycol 4000, the addition of which greatly improved the chiral separation of the enantiomers. The parameters of chiral separation capabilities were also investigated, including resolutions, theoretical plates, capacity factors, apparent mobilities and retention times. This experiment proves this method a success and that the polyethylene glycol 4000 plays an important role in chiral separation when β-cyclodextrin exists.

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Resolution of Chiral Drugs

Cited by 6 publications

References 95 publications

A Simple Method for Resolution ofEndo‐/Exo‐Monoesters ofTrans‐Norborn‐5‐Ene‐2,3‐Dicarboxylic Acids Into Their Enantiomers

A Simple Method for Resolution ofEndo‐/Exo‐Monoesters ofTrans‐Norborn‐5‐Ene‐2,3‐Dicarboxylic Acids Into Their Enantiomers

Exploiting the Power of Stereochemistry in Drugs: An Overview of Racemic and Enantiopure Drugs

Capillary Electrophoresis Separation of the Six Pairs of Chiral Pharmaceuticals Enantiomers

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