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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/09/11 17:09:23」(JST)

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This article is about the concept in chemistry. For a discussion of enantiomers in mathematics, see Chirality (mathematics).

(S)-(+)-lactic acid (left) and (R)-(–)-lactic acid (right) are nonsuperposable mirror images of each other

In chemistry, an enantiomer (/ɨˈnæntɪ.ɵmər/ ə-NAN-tee-ə-mər; from the Greek ἐνάντιος, opposite, and μέρος, part or portion) is one of two stereoisomers that are mirror images of each other that are non-superposable (not identical), much as one's left and right hands are the same except for opposite orientation.^[1]

Organic compounds that contain a chiral carbon usually have two non-superposable structures. These two structures are mirror images of each other and are, thus, commonly called enantiomorphs (enantio = opposite ; morph = form), hence this structural property is now commonly referred to as enantiomerism.

Enantiopure compounds refer to samples having, within the limits of detection, molecules of only one chirality.^[2]

Enantiomers have, when present in a symmetric environment, identical chemical and physical properties except for their ability to rotate plane-polarized light (+/−) by equal amounts but in opposite directions (although the polarized light can be considered an asymmetric medium). A mixture of equal parts of an optically active isomer and its enantiomer is termed racemic and has zero net rotation of plane-polarized light because the positive rotation of each (+) form is exactly counteracted by the negative rotation of a (−) one.

Enantiomers of each other often show different chemical reactions with other substances that are also enantiomers. Since many molecules in the bodies of living beings are enantiomers themselves, there is often a marked difference in the effects of two enantiomers on living beings. In drugs, for example, often only one of a drug's enantiomers is responsible for the desired physiologic effects, while the other enantiomer is less active, inactive, or sometimes even responsible for adverse effects.

Owing to this discovery, drugs composed of only one enantiomer ("enantiopure") can be developed to enhance the pharmacological efficacy and sometimes do away with some side effects. An example of this kind of drug is eszopiclone (Lunesta), which is enantiopure and therefore is given in doses that are exactly 1/2 of the older, racemic mixture called zopiclone. In the case of eszopiclone, the S enantiomer is responsible for all the desired effects, though the other enantiomer seems to be inactive; while an individual must take 2 mg of zopiclone to get the same therapeutic benefit as they would receive from 1 mg of eszopiclone, that appears to be the only difference between the two drugs.

Naming conventions[edit source | edit]

Main article: Chirality (chemistry)#Naming conventions

Criterion of enantiomerism[edit source | edit]

Fischer projection of meso-tartaric acid

Most compounds that contain one or more asymmetric carbon atoms show enantiomerism. But this is not always true.

There are a few known compounds that do have asymmetric carbons, but, being non-dissymmetric with respect to the whole molecule, do not show enantiomerism. Thus, meso tartaric acid has two asymmetric carbons but samples still exhibit optically inactivity because the two halves of the molecule are equal and opposite to each other, and thus is superimposable on its geometric mirror image.

Examples[edit source | edit]

Enantiomers of mecoprop (2-(4-chloro-2-methylphenoxy)propanoic acid)

Enantiomers of citalopram. The top is (R)-citalopram and the bottom is (S)-citalopram.

An example of such an enantiomer is the sedative thalidomide. It was sold in a number of countries across the world from 1957 until 1961, when it was withdrawn from the market after being found to be a cause of birth defects.

In the herbicide mecoprop, the carboxyl group and the hydrogen atom on the central C-atom are exchanged (with the screen as plane of symmetry). After rotating one of the isomers 180 degrees (in the same plane), the two are still mirror images of each other. The mirror image of each enantiomer is superposable on the other enantiomer.

Another example is the antidepressant drugs escitalopram and citalopram. Citalopram is a racemate [1:1 mixture of (S)-citalopram and (R)-citalopram]; escitalopram [(S)-citalopram] is a pure enantiomer. The dosages for escitalopram are typically 1/2 of those for citalopram.

Enantioselective preparations[edit source | edit]

See also: chiral resolution and asymmetric synthesis

There are two main strategies for the preparation of enantiopure compounds. The first is known as chiral resolution. This method involves preparing the compound in racemic form, and separating it into its isomers. In his pioneering work, Louis Pasteur was able to isolate the isomers of tartaric acid because they crystallize from solution as crystals each with a different symmetry. A less common method is by enantiomer self-disproportionation.

The second strategy is asymmetric synthesis: the use of various techniques to prepare the desired compound in high enantiomeric excess. Techniques encompassed include the use of chiral starting materials (chiral pool synthesis), the use of chiral auxiliaries and chiral catalysts, and the application of asymmetric induction. The use of enzymes (biocatalysis) may also produce the desired compound.

Enantioconvergent synthesis is the synthesis of one enantiomer from a racemic precursor molecule utilizing both enantiomers. Thus, the two enantiomers of the reactant produce a single enantiomer of product.

Enantiopure medications[edit source | edit]

Main article: Enantiopure drug

Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers. In some cases, the enantiomers have genuinely different effects. In other cases, there may be no clinical benefit to the patient. In some jurisdictions, single-enantiomer drugs are separately patentable from the racemic mixture.^[3] It is possible that both enantiomers are active. Or, it may be that only one is active, in which case separating the mixture has no objective benefits, but extends the drug's patentability.^[4]

Quasi-enantiomers[edit source | edit]

These molecular species are not strictly enantiomers, but they behave as if they are. Quasi-enantiomers have applications in parallel kinetic resolution (see kinetic resolution).^[5]

References[edit source | edit]

^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "enantiomer".
^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "enantiomerically pure (enantiopure)".
^ http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2009/11/news_detail_000083.jsp&jsenabled=true
^ Merrill Goozner (2004). The $800 Million Pill: The Truth Behind the Cost of New Drugs (excerpt). University of California Press. ISBN 0-520-23945-8.
^ G.S. Coumbarides, M. Dingjan, J. Eames, A. Flinn, J. Northen and Y. Yohannes, Tetrahedron Lett. 46 (2005), p. 2897er

External links[edit source | edit]

chemwiki:stereoisomerism

English Journal

Enantiomer-specific profenofos-induced cytotoxicity and DNA damage mediated by oxidative stress in rat adrenal pheochromocytoma (PC12) cells.

Lu X, Yu C.Author information College of Materials and Environmental Engineering, Hangzhou Dianzi University, Hangzhou, 310018, China.AbstractRecent studies have shown that chiral pesticides could enantioselectively induce cytotoxicity and genotoxicity. However, investigations on molecular mechanisms of enantioselective toxicity of pesticides are limited. In this study, the role of oxidative stress in enantiomer-specific, profenofos (PFF)-induced cytotoxicity and genotoxicity was investigated using PC12 cells. The results demonstrated that PFF enantioselectively reduced cell viability and induced DNA damage in PC12 cells. A concentration- and time-dependent significant induction of reactive oxygen species (ROS), malondialdehyde and gene expression encoding antioxidant enzyme (Cu-ZnSOD, GST and CAT) and stress protein (HSP 70 and HSP 90) was observed in (-)-PFF, whereas (+)-PFF and rac-PFF exhibited these effects to lesser degrees. Pre-treatment with vitamin E (600 μM) caused a significant attenuation in the toxic effect; reversing subsequent PFF-induced elevation of ROS and malondialdehyde (MDA) levels, further strengthening the involvement of oxidative stress in PFF-mediated toxicity. In addition, the results also showed that PFF-dependent ROS accumulation, MDA release and oxidative stress gene expression preceded the loss of cell viability and induction of DNA damage, and already significantly changed at concentrations which are not yet cytotoxic or genotoxic. These results indicate that oxidative stress may contribute to PFF-induced toxicity and that it was not a consequence of it. Copyright © 2013 John Wiley & Sons, Ltd.
Journal of applied toxicology : JAT.J Appl Toxicol.2014 Feb;34(2):166-75. doi: 10.1002/jat.2847. Epub 2013 Mar 13.
Recent studies have shown that chiral pesticides could enantioselectively induce cytotoxicity and genotoxicity. However, investigations on molecular mechanisms of enantioselective toxicity of pesticides are limited. In this study, the role of oxidative stress in enantiomer-specific, profenofos (PFF)
PMID 23495063

Homology modeling and docking studies of BjGL, a novel (+) gamma-lactamase from Bradyrhizobium japonicum.

Song D1, Zhu S1, Li X2, Zheng G3.Author information 1State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China.2Beijing Institute of Pharmacology and Toxicology, Beijing, People's Republic of China.3State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, People's Republic of China. Electronic address: zhenggj@mail.buct.edu.cn.Abstract(+) Gamma-lactamases are enantioselective hydrolysis enzymes that can be used to produce optically pure (-) gamma-lactam, an important pharmaceutical intermediate for the anti-AIDS drug Abacavir. In this study, homology modeling and molecular dynamic simulation studies of a 3D homology model of BjGL, a novel (+) gamma-lactamase from Bradyrhizobium japonicum, were constructed and refined. The specific substrate (+) gamma-lactam and its enantiomer (-) gamma-lactam which can not be hydrolyzed was docked into the active site respectively, and the catalytic triad and other crucial residues that participate in the formation of the hydrophobic binding pocket, hydrogen bonds, and the oxyanion hole were identified. Furthermore, possible reasons for the high diastereoselectivity of BjGL binding with the substrate are proposed.
Journal of molecular graphics & modelling.J Mol Graph Model.2014 Feb;47:1-7. doi: 10.1016/j.jmgm.2013.10.006. Epub 2013 Oct 24.
(+) Gamma-lactamases are enantioselective hydrolysis enzymes that can be used to produce optically pure (-) gamma-lactam, an important pharmaceutical intermediate for the anti-AIDS drug Abacavir. In this study, homology modeling and molecular dynamic simulation studies of a 3D homology model of BjGL
PMID 24215997

A pair of chiral fluorescent sensors for enantioselective recognition of mandelate in water.

Xu KX, Kong HJ, Zu FL, Yang L, Wang CJ.Author information Institute of Fine Chemical and Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, China. Electronic address: xukx@henu.edu.cn.AbstractA pair of chiral compounds S-1 and R-1 derived from (1S, 2S) or (1R, 2R)-1, 2-diphenylethane-1, 2-diamine were designed and synthesized, the interactions of S-1 and R-1 with mandelate were studied in H2O (0.01 M HEPES buffer, pH=7.4) by fluorescence titration experiments. The sensors S-1 and R-1 were found to present enantioselective fluorescent sensing ability to mandelate. The results indicated that the sensors S-1 and R-1 were very promising to be used as fluorescent sensors in determining the enantiomeric composition of mandelate in H2O.
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2014 Jan 24;118:811-5. doi: 10.1016/j.saa.2013.09.083. Epub 2013 Oct 8.
A pair of chiral compounds S-1 and R-1 derived from (1S, 2S) or (1R, 2R)-1, 2-diphenylethane-1, 2-diamine were designed and synthesized, the interactions of S-1 and R-1 with mandelate were studied in H2O (0.01 M HEPES buffer, pH=7.4) by fluorescence titration experiments. The sensors S-1 and R-1 wer
PMID 24157333

Japanese Journal

ENANTIOSELECTIVE SYNTHESIS OF CIS- AND TRANS-2-METHYL-6-NONYLPIPERIDINES : ALKALOIDS SOLENOPSIN AND ISOSOLENOPSIN (Dedicated to Professor Dr. Ei-ichi Negishi on the occasion of his 77th birthday)

Medjahdi Mohamed,Gonzalez-Gomez Jose Carlos,Foubelo Francisco
Heterocycles : an international journal for reviews and communications in heterocyclic chemistry 86(1), 727-734, 2012-12-31
NAID 40019534435

ENANTIOSELECTIVE MUKAIYAMA-ALDOL REACTION BETWEEN ENOL SILANES AND KETOMALONATE CATALYZED BY THE COPPER(？) COMPLEX OF TIPS-SUBSTITUTED BIS-OXAZOLINE (Dedicated to Professor Dr. Ei-ichi Negishi on the occasion of his 77th birthday)

Desimoni Giovanni,Faita Guiseppe,Livieri Alessandro
Heterocycles : an international journal for reviews and communications in heterocyclic chemistry 86(1), 669-677, 2012-12-31
NAID 40019534335