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 ( ə-NAN-tee-ə-mər; from Greek ἐνάντιος (enantíos), meaning "opposite", and μέρος (méros), meaning "part") 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 being reversed along one axis (the hands cannot be made to appear identical simply by reorientation).[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]
When present in a symmetric environment, enantiomers have 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 biological molecules are enantiomers themselves, there is sometimes a marked difference in the effects of two enantiomers on biological organisms. 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.
Contents
- 1 Naming conventions
- 2 Criterion of enantiomerism
- 3 Examples
- 4 Enantioselective preparations
- 5 Enantiopure medications
- 6 Quasi-enantiomers
- 7 History of enantiomers
- 8 See also
- 9 References
- 10 External links
Naming conventions
Main article: Chirality (chemistry) § Naming conventions
Criterion of enantiomerism
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 optical inactivity because each of the two halves of the molecule is equal and opposite to the other and thus is superimposable on its geometric mirror image.
Examples
Structures of the two enantiomeric forms (
S left,
R right) of mecoprop
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. The inactive enantiomer (as a sedative), unavoidably[3] present in equal quantities as the active, was the cause of the defects.[4]
The herbicide mecoprop is a racemic mixture, with the (R)-(+)-enantiomer ("Mecoprop-P", "Duplosan KV") possessing the herbicidal activity.[5]
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
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
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.[6] 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.[7]
Quasi-enantiomers
These molecular species are not strictly enantiomers, but they behave as if they are. Quasi-enantiomers have applications in parallel kinetic resolution.[8]
History of enantiomers
Since 1812, it had been known that certain molecules are optically active. In 1848, Louis Pasteur worked with samples of tartaric acid obtained as a by-product of wine-making. He observed two ammonium salt crystals: one, tartaric acid, was optically active and dextrorotatory, and the other, paratartaric acid (a racemic mixture), was optically inactive. Observing the latter with a microscope, he realized it was made of two types of crystals. He separated the racemic mixture manually, with a pair of tweezers, and redissolved both types of crystal, finding the polarization of light of one of them was complementary to the other (one was dextrorotatory and the other levorotatory).[9]
See also
- Stereochemistry
- Dynamic stereochemistry
- Chirality (chemistry)
- Chirotechnology
- Diastereomers
- Stereogenic
- Atropisomerism
- Antipode (chemistry)
References
- ^ 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)".
- ^ Knoche, B; Blaschke, G. "Investigations on the in vitro racemization of thalidomide by high-performance liquid chromatography". Journal of Chromatography A (Elsevier) 666 (1-2): 235–240. doi:10.1016/0021-9673(94)80385-4.
- ^ Fundamentals of Biochemistry. p. 89. ISBN 0-471-21495-7.
- ^ G. Smith, C. H. L. Kennard, A. H. White and P. G. Hodgson (April 1980). "(±)-2-(4-Chloro-2-methylphenoxy)propionic acid (mecoprop)". Acta Cryst. B36 (4): 992–994. doi:10.1107/S0567740880005134.
- ^ 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
- ^ Johnson, Ally William; Invitation to Organic Chemistry, Jones & Bartlett Learning, 1998, p 622 ISBN 978-0763704322 Google books
External links
|
Concepts in asymmetric synthesis
|
|
| Chirality types |
- Chirality
- Stereocenter
- Planar chirality
- Chiral ligand
- Axial chirality
- Supramolecular chirality
- Inherent chirality
|
|
| Chiral molecules |
- Stereoisomer
- Enantiomer
- Diastereomer
- meso compound
- racemic mixture
- Enantiomeric excess (ee)
- Diastereomeric excess (de)
|
|
| Analysis |
- Optical rotation
- Chiral derivatizing agents
- NMR spectroscopy of stereoisomers
- Ultraviolet-visible spectroscopy of stereoisomers
|
|
| Chiral resolution |
- Recrystallization
- Kinetic resolution
- Chiral column chromatography
- Diastereomeric recrystallization
|
|
| Reactions |
- Asymmetric induction
- Chiral pool synthesis
- Chiral auxiliaries
- Asymmetric catalysis
- Organocatalysis
- Biocatalysis
|
|
