Diastereomer

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Diastereomers that are also epimers
D-threose.svg D-erythrose.svg
DThreose Fischer.svg DErythrose Fischer.svg
D-Threose D-Erythrose

In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer.[1] Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have different configurations at one or more (but not all) of the equivalent (related) stereocenters and are not mirror images of each other.[2] When two diastereoisomers differ from each other at only one stereocenter, they are epimers. Each stereocenter gives rise to two different configurations and thus typically increases the number of stereoisomers by a factor of two.

Diastereomers differ from enantiomers in that the latter are pairs of stereoisomers that differ in all stereocenters and are therefore mirror images of one another.[3] Enantiomers of a compound with more than one stereocenter are also diastereomers of the other stereoisomers of that compound that are not their mirror image (that is, excluding the opposing enantiomer). Diastereomers have different physical properties (unlike most aspects of enantiomers) and often different chemical reactivity.

Diastereomers differ not only in physical properties but also in chemical reactivity — how a compound reacts with others. Glucose and galactose, for instance, are diastereomers. Even though they share the same molar weight, glucose is more stable than galactose. This difference in stability causes galactose to be absorbed slightly faster than glucose in human body.[4][5]

Diastereoselectivity is the preference for the formation of one or more than one diastereomer over the other in an organic reaction. In general, stereoselectivity is contributed to torsional and steric interactions in the stereocenter resulting from electrophiles approaching the stereocenter in reaction.[6]

Syn / anti[edit]

When the single bond between the two centres is free to rotate, cis/trans descriptors become invalid. Two widely accepted prefixes used to distinguish diastereomers on sp³-hybridised bonds in an open-chain molecule are syn and anti. Masamune proposed the descriptors which work even if the groups are not attached to adjacent carbon atoms. It also works regardless of CIP priorities. Syn describes groups on the same face while anti describes groups on opposite faces. The concept applies only to the Zigzag projection. The descriptors only describe relative stereochemistry rather than absolute stereochemistry. All isomers are same.

Erythro / threo[edit]

Two older prefixes still commonly used to distinguish diastereomers are threo and erythro. In the case of saccharides, when drawn in the Fischer projection the erythro isomer has two identical substituents on the same side and the threo isomer has them on opposite sides.[7] When drawn as a zig-zag chain, the erythro isomer has two identical substituents on different sides of the plane (anti). The names are derived from the diastereomeric four-carbon aldoses erythrose (a syrup) and threose (melting point 126 °C). These prefixes are not recommended for use outside of the realm of saccharides because their definitions can lead to conflicting interpretations.[8]

Another threo compound is threonine, one of the essential amino acids. The erythro diastereomer is called allothreonine.

L-Threonin - L-Threonine.svg D-Threonine.svg
L-Threonine (2S,3R) and D-Threonine (2R,3S)
L-allo-Threonine.svg D-allo-Threonine.svg
L-Allothreonine (2S,3S) and D-Allothreonine (2R,3R)

Multiple stereocenters[edit]

If a molecule contains two asymmetric centers, there are up to four possible configurations, and they cannot all be non-superposable mirror images of each other. The possibilities for different isomers continue to multiply as more stereocenters are added to a molecule. In general, the number of stereoisomers of a molecule can be determined by calculating 2n, where n = the number of chiral centers in the molecule. This holds true except in cases where the molecule has meso forms. These meso compounds are molecules that contain stereocenters, but possess an internal plane of symmetry allowing it to be superposed on its mirror image. These equivalent configurations cannot be considered diastereomers.[9]

For n = 3, there are eight stereoisomers. Among them, there are four pairs of enantiomers: R,R,R and S,S,S; R,R,S and S,S,R; R,S,S and S,R,R; and R,S,R and S,R,S. There are many more pairs of diastereomers, because each of these configurations is a diastereomer with respect to every other configuration excluding its own enantiomer (for example, R,R,R is a diastereomer of R,R,S; R,S,R; and R,S,S). For n = 4, there are sixteen stereoisomers, or eight pairs of enantiomers. The four enantiomeric pairs of aldopentoses and the eight enantiomeric pairs of aldohexoses (subsets of the five- and six-carbon sugars) are examples of sets of compounds that differ in this way.

Diastereomerism at a Double Bond[edit]

Double bond isomers are always considered diastereomers, not enantiomers. Diastereomerism can also occur at a double bond, where the cis vs trans relative positions of substituents give two non-superposable isomers. Many conformational isomers are diastereomers as well.

In the case of diastereomerism occurring at a double bond, E-Z, or entgegen and zusammen (German), is used in notating nomenclature of alkenes.[10]

Applications[edit]

As stated previously, two diastereomers will not have identical chemical properties. This knowledge is harnessed in chiral synthesis to separate a mixture of enantiomers. This is the principle behind chiral resolution. After preparing the diastereomers, they are separated by chromatography or recrystallization. Note also the example of the stereochemistry of ketonization of enols and enolates.

See also[edit]

References[edit]

  1. ^ IUPAC "Gold Book" diastereoisomerism  doi:10.1351/goldbook.D01679
  2. ^ Garrett, R.H.; Grisham, C.M. (2005), Biochemistry 3rd ed., Belmont CA: Thomson, p. 205, ISBN 0-534-41020-0.
  3. ^ IUPAC "Gold Book" enantiomer  doi:10.1351/goldbook.E02069
  4. ^ McCance, Robert Alexander; Madders, Kate (1930). "The comparative rates of absorption of sugars from the human intestine". Biochemical Journal. 24 (3): 795–804. doi:10.1042/bj0240795. ISSN 0264-6021. PMC 1254520. PMID 16744419.
  5. ^ Chao, Hsi-Chun; McLuckey, Scott A. (2020-10-06). "Differentiation and Quantification of Diastereomeric Pairs of Glycosphingolipids using Gas-phase Ion Chemistry". Analytical Chemistry. 92 (19): 13387–13395. doi:10.1021/acs.analchem.0c02755. ISSN 0003-2700. PMC 7544660. PMID 32883073.
  6. ^ Lavinda, Olga; Witt, Collin H.; Woerpel, K. A. (2022-03-28). "Origin of High Diastereoselectivity in Reactions of Seven-Membered-Ring Enolates". Angewandte Chemie International Edition in English. 61 (14): e202114183. doi:10.1002/anie.202114183. ISSN 1521-3773. PMC 8940697. PMID 35076978.
  7. ^ Modern physical organic chemistry Eric V. Anslyn,Dennis A. Dougherty 2006
  8. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "erythro, threo". doi:10.1351/goldbook.E02212
  9. ^ Merad, Jérémy; Candy, Mathieu; Pons, Jean-Marc; Bressy, Cyril (May 2017). "Catalytic Enantioselective Desymmetrization of Meso Compounds in Total Synthesis of Natural Products: Towards an Economy of Chiral Reagents". Synthesis. 49 (9): 1938–1954. doi:10.1055/s-0036-1589493. ISSN 0039-7881.
  10. ^ Brown, William (2018). Organic Chemistry (8th ed.). United States: Cengage Learning. pp. 138–142. ISBN 9781305580350.