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5.12: Chirality in Nature and Chiral Environments

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    After completing this section, you should be able to explain how chiral molecules in nature can have such dramatically different biological properties.

    Some Chiral Organic Molecules

    There are a number of important biomolecules that could occur as enantiomers, including amino acids and sugars. In most cases, only one enantiomer occurs naturally (although some fungi, for example, are able to produce mirror-image forms of these compounds). We will look later at some of these biomolecules, but first we will look at a compound that occurs naturally in both enantiomeric forms.

    Carvone is a secondary metabolite. That means it is a naturally-occurring compound that is not directly connected to the very basic functions of a cell, such as self-replication or the production of energy. The role of secondary metabolites in nature is often difficult to determine. However, these compounds often play roles in self-defense, acting as deterrents against competitor species in a sort of small-scale chemical warfare scenario. They are also frequently used in communications; this role has been studied most extensively among insects, which use lots of compounds to send information to each other.

    Wedge-dash structure of (S)-carvone and (R)-carvone. The physical properties of both are listed (both are oils at 25 degrees celsius; both have a boiling point of 230-231 degrees celsius; both have a density of 0.965 g/mL; both have n = 1.4988; and both are insoluble in water, but miscible in EtOH and MeOH). they only differ in their optical rotation, where [alpha]D of (S)-carvone is +61.2 degrees and [alpha]D of (R)-carvone is -62.46 degrees
    Figure \(\PageIndex{1}\): The two naturally-occurring enantiomers of carvone.

    Carvone is produced in two enantiomeric forms. One of these forms, called (-)-carvone, is found in mint leaves, and it is a principal contributor to the distinctive odor of mint. The other form, (+)-carvone, is found in caraway seeds. This form has a very different smell, and is typically used to flavor rye bread and other Eastern European foods.

    Note that (+)-carvone is another name for (S)-carvone. The (+) designation is based on its positive optical rotation value, which is experimentally measured. This means the (-)-carvone is (R)-carvone and would have a negative optical rotation value.

    How different, exactly, are these two compounds, (+)- and (-)-carvone? Are they completely different isomers, with different physical properties? In most ways, the answer is no. These two compounds have the same appearance (colorless oil), the same boiling point (230 °C), the same refractive index (1.499) and specific gravity (0.965). However, they have optical rotations that are almost exactly opposite values.

    • Two enantiomers have the same physical properties.
    • Enantiomers have opposite optical rotations.

    Clearly they have different biological properties; since they have slightly different odors, they must fit into slightly different nasal receptors, signaling to the brain whether the person next to you is chewing a stick of gum or a piece of rye bread. This is much like how a left hand only fits into a left handed baseball glove and not into a right handed one. Receptors which allow for a biological effect, in this case to perceive a certain smell, are often chiral and will only allow one enantiomer of a chiral substrate to fit. An example of this is shown in the figure below. The receptor as a complementary three-dimension shape to allow the R configuration of the chiral substrate to fit. When the S configuration of the chiral substrate attempts to fit the configuration does not match that of the receptor as shown in the second drawing where the bottom two groups do not fit the receptor site.


    Chiral Environments

    In the previous section, enzymes were shown to be capable of converting a prochiral substrate into a single enantiomer product. Enzymes can provides such an effect because they create a chiral environment. The figure below shows a prochiral substrate. The magenta and blue balls represent substituents while the two green balls represent two of the same substituent which is available for a given reaction. One of these substituents is pro-R and the other is pro-S. Without the presence of a chiral environment the two green substituents are chemically identical. However, as the prochiral molecule interacts with the chiral environment provided by an enzyme the two green substituents become chemically distinct. Despite being achiral, the prochiral molecule can only interact with the chiral environment in one specific position. The figure below shows that the pro-S green substituent of the prochiral molecule is protected by the enzyme, while the pro-R green substituent is exposed and can undergo a reaction. In this case the enzyme would provide a product that is predominantly the R enantiomer.

    Chiral Environment.svg

    Exercise \(\PageIndex{1}\)

    The following are three molecules found in nature. Please identify four chiral centers in each, mark them with asterisks, and identify each center as having a R or S configuration. Each molecule contains more than four chiral centers.

    a) The following is the structure of dysinosin A, a potent thrombin inhibitor that consequently prevents blood clotting.

    structure of dysinosin A.svg

    b) Ginkgolide B (below) is a secondary metabolite of the ginkgo tree, extracts of which are used in Chinese medicine.

    structure of ginkgolide B.svg

    c) Sanglifehrin A, shown below, is produced by a bacteria that may be found in the soil of coffee plantations in Malawi. It is also a promising candidate for the treatment of organ transplant patients owing to its potent immuno-suppressant activity.

    structure of Sanglifehrin A.svg



    structure of dysinosin A with chiral centers labeled.svg


    structure of ginkgolide B with chiral centers labeled.svg


    structure of sanglifehrin A with chiral centers labeled.svg

    structure of thalidomide.svg
    Figure \(\PageIndex{2}\): Thalidomide.

    There are other reasons that we might concern ourselves with an understanding of enantiomers, apart from dietary and olfactory preferences. Perhaps the most dramatic example of the importance of enantiomers can be found in the case of thalidomide. Thalidomide was a drug commonly prescribed during the 1950's and 1960's in order to alleviate nausea and other symptoms of morning sickness. In fact, only one enantiomer of thalidomide had any therapeutic effect in this regard. The other enantiomer, apart from being therapeutically useless in this application, was subsequently found to be a teratogen, meaning it produces pronounced birth defects. This was obviously not a good thing to prescribe to pregnant women. Workers in the pharmaceutical industry are now much more aware of these kinds of consequences, although of course not all problems with drugs go undetected even through the extensive clinical trials required in the United States. Since the era of thalidomide, however, a tremendous amount of research in the field of synthetic organic chemistry has been devoted to methods of producing only one enantiomer of a useful compound and not the other. This effort probably represents the single biggest aim of synthetic organic chemistry through the last quarter century.

    • Enantiomers may have very different biological properties.
    • Obtaining enantiomerically pure compounds is very important in medicine and the pharmaceutical industry.

    5.12: Chirality in Nature and Chiral Environments is shared under a CC BY-SA 4.0 license and was authored, remixed, and/or curated by Chris Schaller, Steven Farmer, Dietmar Kennepohl, Layne Morsch, John Roberts, Marjorie C. Caserio, & Marjorie C. Caserio.