What is Chirality
In chemistry, chirality refers to how a molecule's components are arranged, in space, about a central atom (or atoms). Chiral molecules (and objects as well) lack symmetry and therefore cannot be superimposed on their mirror images – or put more simply, you can't wear a left-hand glove on your right hand or a right shoe on your left foot !!
Your hands (and feet) are 'non-superimposible' mirror images of each other. Hold your hands in front of you, palms down. You can see that you would get the same view if you pointed your thumb at a mirror with the palm of your hand facing downward.
OK, they are mirror images of each other, but why are they 'non-superimposable' ? Well, try to exactly match-up, or 'superimpose' your two hands. You'll have to have your palms pointing in the same direction, but what happens ? your thumbs are pointing in opposite directions, i.e. they are non-superimposable.
Your hands are chiral. In fact, the word 'chiral' comes from the Greek word for hand.
In the example below we have a central carbon atom to which we attach four other atoms such that the attachment points are as far apart as possible. This geometry is known as a tetrahedron.
Now let's switch the positions of two of the attached molecules.
It's not immediately apparent that the two molecules are different in any way. In fact they would possess exactly the same chemical and physical properties, but their chirality differs as the following figure shows.
Like your hands, the two 'molecules' are mirror images that cannot be superimposed on one another. Each of these chiral forms is called an isomer.
Generally speaking, chirality is a property of carbon compounds which have four different components, or substituents, attached to one carbon. This central carbon atom is known as a chiral center or center of chirality. Many molecules have two or more chiral centers. Proteins, which are made of individually-chiral amino acid building blocks, may contain hundreds of chiral centers.
While nature usually only creates one chiral form of a molecule, man-made chemical compounds are almost always either achiral (lacking chirality), or they contain equal quantities of both mirror-image forms. Such mixtures are known as racemates or racemic mixtures.
Why chirality is important
Chirality is critical in the biochemistry of natural products and drugs. Most biomolecules – proteins, hormones, nutrients, sugars, fats, and many others – are chiral. In nature, a molecules' chirality is often as important as its chemical makeup.
For example the natural flavoring compound carvone is chiral. One chiral form of carvone tastes like rye, while the other form tastes like spearmint. Our taste buds recognize the two chiral forms as different compounds.
Chirality is important for pharmaceuticals because the body recognizes chirality (as the example of our taste buds illustrates). The most famous (or infamous) example of this is thalidomide, a drug used during the 1950s as a sleeping pill and to relieve morning sickness in pregnant women. Thalidomide is chiral, and both chiral forms were present in the manufactured drug. Some studies suggest that one chiral form of thalidomide was responsible for its beneficial therapeutic effect, while the other caused severe birth defects.
Most of the time both chiral forms of a drug can be taken safely without serious side effects. In some situations one chiral form is active and the other is not. To improve the effectiveness of such drugs and to reduce possible side effects from the "wrong" chiral form, many of today’s newer pharmaceuticals are manufactured as pure chiral isomers. The challenge is developing a cost-effective manufacturing process for single isomer chiral drugs.
Meeting the Challenge
There are only three practical routes to chiral molecules: find them in nature, modify a naturally-occurring chiral molecule, or create them through chiral synthesis (also called asymmetric synthesis).
Until recently most of our medicines were natural products – derived from plants. Morphine, extracted from poppy plants, is an example. Beginning in the 19th century, chemists began modifying natural molecules to exploit nature’s ability to create unique chemical structures with built-in chirality. About half of all the medicines sold today are based on natural compounds, many of which are chiral.
Modern drug-making increasingly relies on structures which do not resemble natural products. Making these compounds in chiral form requires a chiral synthesis. Chiral synthesis is most often carried out using a chiral catalyst. Catalysts are helper molecules that make chemical reactions proceed more easily but are not themselves consumed in the reaction. Thus, catalysts are used over and over during a chemical process.
Chemists use catalysts to make almost everything, from gasoline to rubber. Chiral catalysts have two functions: to help carry out the chemical reaction, and to transfer chirality to the product.
Where Chiral Quest Fits In
Chiral Quest provides pharmaceutical manufacturers with a broad, versatile offering of chiral catalysts for creating chiral molecules. Chiral Quest customers use these catalysts to achieve superior chemical and chiral purity for dozens of important chiral pharmaceutical intermediates. Chiral Quest also provides chiral building blocks that are further transformed into the final chiral drugs by its customers.
Chiral Quest’s chiral building blocks and chiral catalysts offer the highest-value, lowest-cost route to the wealth of chemical diversity critical to pharmaceutical research, development and manufacturing.
