Enantiomer

Overview

In chemistry, enantiomers (from the Greek ἐνάντιος, opposite, and μέρος, part or portion) are stereoisomers that are nonsuperimposable complete mirror images of each other, much as one's left and right hands are "the same" but opposite.

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. A mixture of equal parts of an optically active isomer and its enantiomer is termed racemic and has a net rotation of plane-polarized light of zero.

Two symmetrical enantiomers often do have different chemical properties related to 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 symmetrical enantiomers on living beings, including human beings.

Naming conventions

There are several conventions used for naming chiral compounds, all displayed as a prefix before the chemical name of the substance:

(+)- versus (−)-; also written d- vs. l-

- based on the substance's ability to rotate polarized light.

D- vs. L-

- based on the actual geometry of each enantiomer, with the version synthesized from naturally occurring (+)-glyceraldehyde being considered the D- form.

(R)- vs. (S)-

- based on the actual geometry of each enantiomer, using the Cahn-Ingold-Prelog priority rules to classify the form. Molecules with multiple stereogenic centers will have a corresponding number of letters; e.g. natural (+)-α-tocopherol is R,R,R-α-tocopherol.

The (+)- vs. (−)- convention is the only one based on optical properties. The other two conventions are based on the actual geometry of each enantiomer. There is no correspondence between any convention. In nature, many chiral substances are only produced in one optical form, while (most) man-made chiral substances are racemic mixtures. The purity of enantiomers can be determined by optical rotation.

More definitions

Any non-racemic chiral substance is called scalemic.
A chiral substance is enantiopure or homochiral when only one of two possible enantiomers is present.
A chiral substance is enantioenriched or heterochiral when an excess of one enantiomer is present but not to the exclusion of the other.
Enantiomeric excess or ee is a measure for how much of one enantiomer is present compared to the other. For example, in a sample with 40% ee in R, the remaining 60% is racemic with 30% of R and 30% of S, so that the total amount of R is 70%.

Enantioselective preparations

Several strategies exist for the preparation of enantiopure compounds. This first method is the separation of a racemic mixture into its isomers, a process called chiral resolution. Louis Pasteur in his pioneering work 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.

Other methods are chiral pool synthesis: using chiral starting material and maintaining the chirality; asymmetric induction, the use of chiral auxiliaries, chiral reagents, and chiral catalysts to favor the reaction of one diastereomer over another, and the use of biocatalysts.

Enantioconvergent synthesis is the the synthesis of one enantiomer from a racemic precursor molecule utilizing both enantiomers.

Enantiopure medications

Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed in racemic form and market the individual enantiomers, each of which may have unique properties. For some drugs, such as zopiclone, only one enantiomer (eszopiclone) is active; the FDA has allowed such once-generic drugs to be patented and marketed under another name. In other cases, such as ibuprofen, it is not economically feasible to isolate a single enantiomer from a racemic mixture or to synthesize just the active one, and therefore a racemic mixture is marketed, with an essentially doubled recommended dose.

Examples of racemic mixtures and the corresponding single-enantiomer products that have been marketed include:

Amphetamine (Benzedrine; street amphetamine is also racemic) and dextroamphetamine (Dexedrine)
Bupivacaine (Marcain) and levobupivacaine (Chirocaine)
Cetirizine (Zyrtec / Reactine) and levocetirizine (Xyzal)
Citalopram (Celexa / Cipramil) and escitalopram (Lexapro / Cipralex)
Methylphenidate (Ritalin) and dexmethylphenidate (Focalin)
Modafinil (Provigil) and armodafinil (Nuvigil)
Ofloxacin (Floxin) and levofloxacin (Levaquin)
Omeprazole (Prilosec) and esomeprazole (Nexium)
Salbutamol (Ventolin) and levalbuterol (Xopenex)
Zopiclone (Imovane) and eszopiclone (Lunesta)

Thalidomide is an example of a racemic drug, in which one enantiomer produces a desirable antiemetic effect, whereas the other is toxic and produces a teratogenic side-effect. However, the enantiomers are converted into each other in vivo, so chemical processes may not be used to mitigate its toxicity.