Enantiomer

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

In chemistry,

an enantiomer (/nnt.mr/ -NAN-tee--mr;

from

the

Greek , opposite,

and , part or portion) is one of two stereoisomers that are mirror images of each other that are nonsuperposable (not identical), much as one's left and right hands are the same except for opposite orientation. 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. 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 sometimes 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
By configuration: R- and SFor chemists, the R / S system is the most important nomenclature system for denoting enantiomers, which does not involve a reference molecule such as glyceraldehyde. It labels each chiral center R or S according to a system by which its substituents are each assigned a priority, according to the CahnIngoldPrelog priority rules (CIP), based on atomic number. If the center is oriented so that the lowest-priority of the four is pointed away from a viewer, the viewer will then see two possibilities: If the priority of the remaining three substituents decreases in clockwise direction, it is labeled R (for Rectus, Latin for right), if it decreases in counterclockwise direction, it is S (for Sinister, Latin for left). This system labels each chiral center in a molecule (and also has an extension to chiral molecules not involving chiral centers). Thus, it has greater generality than the D/L system, and can label, for example, an (R,R) isomer versus an (R,S) diastereomers. The R / S system has no fixed relation to the (+)/() system. An R isomer can be either dextrorotatory or levorotatory, depending on its exact substituents. The R / S system also has no fixed relation to the D/L system. For example, the side-chain one of serine contains a hydroxyl group, -OH. If a thiol group, -SH, were swapped in for it, the D/L labeling would, by its definition, not be affected by the substitution. But this substitution would invert the molecule's R / S labeling, because the CIP priority of CH2OH is lower than that for CO2H but the CIP priority of CH2SH is higher than that for CO2H. For this reason, the D/L system remains in common use in certain areas of biochemistry, such as amino acid and carbohydrate chemistry, because it is convenient to have the same chiral label for all of the commonly occurring structures of a given type of structure in higher organisms. In the D/L system, they are nearly all consistent - naturally occurring amino acids are all L, while naturally occurring carbohydrates are nearly all D. In the R / S system, they are mostly S, but there are some common exceptions.

By optical activity: (+)- and ()- or d- and lAn enantiomer can be named by the direction in which it rotates the plane of polarized light. If it rotates the light clockwise (as seen by a viewer towards whom the light is traveling), that enantiomer is labeled (+). Its mirror-image is labeled (). The (+) and () isomers have also been termed d- and l-, respectively (for dextrorotatory and levorotatory). Naming with d- and l- is easy to confuse with D- and L- labeling and is therefore strongly discouraged by IUPAC.

By configuration: D- and LAn optical isomer can be named by the spatial configuration of its atoms. The D/L system, not to be confused with the d- and l-system, see above, does this by relating the molecule to glyceraldehyde. Glyceraldehyde is chiral itself, and its two isomers are labeled D and L (typically typeset in small caps in published work). Certain chemical manipulations can be performed on glyceraldehyde without affecting its configuration, and its historical use for this purpose (possibly combined with its convenience as one of the

smallest commonly used chiral molecules) has resulted in its use for nomenclature. In this system, compounds are named by analogy to glyceraldehyde, which, in general, produces unambiguous designations, but is easiest to see in the small biomolecules similar to glyceraldehyde. One example is the amino acid alanine, which has two optical isomers, and they are labeled according to which isomer of glyceraldehyde they come from. On the other hand, glycine, the amino acid derived from glyceraldehyde, has no optical activity, as it is not chiral (achiral). Alanine, however, is chiral. The D/L labeling is unrelated to (+)/(); it does not indic ate which enantiomer is dextrorotatory and which is levorotatory. Rather, it says that the compound's stereochemistry is related to that of the dextrorotatory or levorotatoryenantiomer of glyceraldehydethe dextrorotatory isomer of glyceraldehyde is, in fact, the D- isomer. Nine of the nineteen L-amino acids commonly found in proteins are dextrorotatory (at a wavelength of 589 nm), and D-fructose is also referred to as levulose because it is levorotatory. A rule of thumb for determining the D/L isomeric form of an amino acid is the "CORN" rule. The groups: COOH, R, NH2 and H (where R is the side-chain) are arranged around the chiral center carbon atom. With the hydrogen atom away from the viewer, if the arrangement of the CORN groups around the carbon atom is center is clockwise, then it is [13] the D form. If the arrangement is counter-clockwise, it is the L form. The L form is the usual one found in natural proteins. For most amino acids, the L form corresponds to an S absolute stereochemistry, but is R instead for certain side-chains.

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

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
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 selfdisproportionation. 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
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. 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.

Quasi-enantiomers
These molecular species are not strictly enantiomers, but they behave as if they are. Quasi-enantiomers have applications in parallel kinetic resolution.