What is chiral? The word "chiral" comes from the Greek "cheir" meaning hand. Try to imagine the left hand in front of the mirror, her reflection is of course the right hand. Now position the left hand and right hand facing down or toward the floor. Then put your left hand on your right hand. Look, the right hand could not diimpitkan with our left hand.
The same is true of certain organic molecules. In Figure 1, can be Alanine compound has two different structures. Assume that A and B are analogous to the left hand and right hand us. A and B are often referred to as stereoisomers (isomer of space) or optical isomers. It must be remembered, an organic molecule is called chiral molecules if there is at least one C atom that binds to four different groups such as Alanine compounds in Figure 1. Chiral molecules have very unique properties, namely optical properties. This means that a chiral molecule has the ability to rotate the plane of polarized light in a device called a polarimeter.
Optical isomer nomenclature system was introduced Chan-Ingold-Prelog who menglasifikasikan chiral C atom as R or S. This nomenclature system is often called the absolute configuration / absolute. For example (2R, 3S) -2.3 dibromo pentane. In this paper will not explain the rules of naming R and S, but the reader can read them at the organic level literature courses. With this nomenclature system of classification introduced two stereoisomers, namely enantiomers and diastereoisomers. Definition of enantiomers and diastereoisomers bit tricky but it will be explained in simple.
(2R, 3S) -2.3 dibromo pentane and (2S, 3R) -2.3 dibromo pentane
(2R, 3S) -2.3 dibromo pentane and (2R, 3R) -2.3 dibromo pentane
Now the following explanation:
If in between a pair of stereoisomers no chiral C atom has the same configuration, the stereoisomers are enantiomers. As the first example of (2R, 3S) -2.3 dibromo pentane and (2S, 3R) -2.3 dibromo pentane.
If in between a pair of stereoisomers there are at least one chiral C atoms having the same configuration, the stereoisomers are diastereoisomers. As a second example (2R, 3S) -2.3 dibromo pentane and (2R, 3R) -2.3 dibromo pentane.
Some communities may be less attention to the optical properties of an organic compound, whereas the chemical reactions in living biological systems are very stereospecific. This means that a stereoisomer would undergo different reactions with her partner stereoisomer in biological systems of living things. In fact, sometimes a stereoisomer will produce different products with stereoisomer partner in living biological systems. Examples are:
Thalidomide drug
This drug is marketed in Europe around the year 1959-1962 as a sedative. This drug has two enantiomers, where the enantiomers are useful as a sedative is (R)-Thalidomide. But pregnant women who consume enantiomernya namely (S)-Thalidomide experienced a problem with fetal limb growth. Occurred at least 2000 cases of birth defects in the 1960s. This is a great tragedy that can not be forgotten in the history of chiral drugs.
Nicotine
(-) Nicotine is reported to be more toxic and dangerous than the (+) Nicotine. Sign "+" direction of rotation of the polarimeter according to state-clockwise, while the sign "-" states the direction of rotation counter-clockwise polarimeter.
Thyroxine
Thyroxine is a hormone produced by the thyroid gland. (-) Thyroxine regulates the body's metabolism, whereas (+) Thyroxine regulation does not produce any effect.
Looking at the facts on the stereochemistry (spatial structure) of an organic compound absolutely must be taken into account in biological reactions of living things. Unfortunately very difficult to produce a pure enantiomers or diastereoisomers. Even 90 percent of synthetic drugs containing chiral compounds are marketed under rasemik until the early 1990s.
Rasemik mixture means a mixture containing a pair of enantiomers in equal amounts. So how do I obtain an enantiomer with enantiomeric excess (EE) is high? Enantiomeric excess means that the configured percentage of the R enantiomer reduced the percentage of spouses who berkonfigurasi S enantiomer in a mixture or vice versa. Before answering that question, keep in mind two basic principles of optical isomers, namely:
A pair of enantiomers having the physical properties (boiling point, solubility, etc.) are similar but differ in the direction of rotation of the polarimeter and interaction with other chiral substances.
A pair of diastereoisomers having the physical properties and the rotation angle polarimeter which differ from each other. In fact often the reaction takes a different way. This means that we can separate a mixture of two diastereoisomers by means of physics (distillation, crystallization, etc.). But can not separate a mixture of two enantiomers by means of physics, for a pair of enantiomers have the same physical properties. In conclusion, we can easily separate a mixture of two diastereoisomers, but it will be difficult to separate a mixture of two enantiomers.
Then how to obtain an enantiomer with high ee? Louis Pasteur is said never to separate the two enantiomers of tartaric Sodium Amoium using tweezers. This can happen because the two enantiomers crystallize separately. This method is often referred to the resolution. This is less effective because not all enantiomers crystallize separately.
So the resolution can not be regarded as a common technique. Another way that is often taken by the chemists is a biochemical route by using enzymes or microorganisms to produce the pure enantiomer. For example, (R)-Nikotina can be obtained by incubating the mixture rasemik (R)-Nikotina and (S)-Nikotina in a container of the bacteria Pseudomonas putida. The bacteria will only oxidize (S)-Nikotina, whereas (R)-Nikotina will remain in the container. Some other products of the biochemical route is Monosodium L-glutamate, L-Lysine and L-Menthol. Nomenclature system of D and L is called the relative configuration. This system is often used in naming the amino acids and carbohydrates.
Unfortunately not all of enantiomers can be produced with high ee through this biochemical route. This is because the specificities of the enzymes and microorganisms. For example, the bacteria Pseudomonas putida can not be used to separate the (+)-Menthol with (-)-Menthol.
The organic chemists such as Ryoji Noyori and William S. Knowles did not lose the sense in solving this problem. William S. Knowles managed to synthesize a compound called (R, R)-DiPAMP (Fig. 2.). It uses the (R, R)-DiPAMP as a ligand to form complex compounds with Rh metal. These complex compounds are very useful in asymmetric hydrogenation processes enamida group. With this complex compound, he managed to synthesize L-DOPA which is very useful in the treatment of Parkinson's disease with a purity of 95 percent ee.
In addition to L-DOPA, the complex compound is also often used to synthesize the acid? alpha-amino acids with high ee, L-Phenilalanin example, L-tryptophan, L-Alanine, L-lysine, etc., except for aspartic acid because it has two adjacent carboxylate groups.
On the other hand, Ryoji Noyori synthesize compounds that are named BINAP (Figure 3.). He used BINAP as a ligand to form complex compounds with metal Ru. These complex compounds are very flexible, because it can be used for asymmetric hydrogenation of alkenes, and enantioselective reduction of ketones are. Actually, the enantioselective reduction of ketones is not new, but the use of transition metals as catalysts for the reduction of ketones is usually difficult and is not enantioselective. Enantioselective means a reaction that produces two enantiomers, in which one enantiomer is produced in greater numbers than the enantiomer partner.
Especially for the reduction of ketones, Ryoji Noyori synthesize (S)-BINAP / (S)-diamine Ru (II) catalyst. With these complex compounds are widely produced chiral drugs with low production costs and high purity. For example, L-DOPS, Levofloxacin, Neobenodine, Fosfomycin, fluoxetine hydrochloride, naproxen, and others. For the record L-DOPS is a precursor of Norepinephrine. Norepinephrine is a neurotransmitter to send signals to the heart and blood vessels.
Both of these discoveries have opened new horizons in science and technology. According to reports, until 2000, sales of chiral drugs in enantiomerically pure form in the world has reached 123 billion U.S. dollars. It is also possible the realization of new discoveries, it is even possible that the Indonesian people will make new breakthroughs. Remember, this story is not over, because science is never dead. Finally, science continues to advance Indonesia.
The same is true of certain organic molecules. In Figure 1, can be Alanine compound has two different structures. Assume that A and B are analogous to the left hand and right hand us. A and B are often referred to as stereoisomers (isomer of space) or optical isomers. It must be remembered, an organic molecule is called chiral molecules if there is at least one C atom that binds to four different groups such as Alanine compounds in Figure 1. Chiral molecules have very unique properties, namely optical properties. This means that a chiral molecule has the ability to rotate the plane of polarized light in a device called a polarimeter.
Optical isomer nomenclature system was introduced Chan-Ingold-Prelog who menglasifikasikan chiral C atom as R or S. This nomenclature system is often called the absolute configuration / absolute. For example (2R, 3S) -2.3 dibromo pentane. In this paper will not explain the rules of naming R and S, but the reader can read them at the organic level literature courses. With this nomenclature system of classification introduced two stereoisomers, namely enantiomers and diastereoisomers. Definition of enantiomers and diastereoisomers bit tricky but it will be explained in simple.
(2R, 3S) -2.3 dibromo pentane and (2S, 3R) -2.3 dibromo pentane
(2R, 3S) -2.3 dibromo pentane and (2R, 3R) -2.3 dibromo pentane
Now the following explanation:
If in between a pair of stereoisomers no chiral C atom has the same configuration, the stereoisomers are enantiomers. As the first example of (2R, 3S) -2.3 dibromo pentane and (2S, 3R) -2.3 dibromo pentane.
If in between a pair of stereoisomers there are at least one chiral C atoms having the same configuration, the stereoisomers are diastereoisomers. As a second example (2R, 3S) -2.3 dibromo pentane and (2R, 3R) -2.3 dibromo pentane.
Some communities may be less attention to the optical properties of an organic compound, whereas the chemical reactions in living biological systems are very stereospecific. This means that a stereoisomer would undergo different reactions with her partner stereoisomer in biological systems of living things. In fact, sometimes a stereoisomer will produce different products with stereoisomer partner in living biological systems. Examples are:
Thalidomide drug
This drug is marketed in Europe around the year 1959-1962 as a sedative. This drug has two enantiomers, where the enantiomers are useful as a sedative is (R)-Thalidomide. But pregnant women who consume enantiomernya namely (S)-Thalidomide experienced a problem with fetal limb growth. Occurred at least 2000 cases of birth defects in the 1960s. This is a great tragedy that can not be forgotten in the history of chiral drugs.
Nicotine
(-) Nicotine is reported to be more toxic and dangerous than the (+) Nicotine. Sign "+" direction of rotation of the polarimeter according to state-clockwise, while the sign "-" states the direction of rotation counter-clockwise polarimeter.
Thyroxine
Thyroxine is a hormone produced by the thyroid gland. (-) Thyroxine regulates the body's metabolism, whereas (+) Thyroxine regulation does not produce any effect.
Looking at the facts on the stereochemistry (spatial structure) of an organic compound absolutely must be taken into account in biological reactions of living things. Unfortunately very difficult to produce a pure enantiomers or diastereoisomers. Even 90 percent of synthetic drugs containing chiral compounds are marketed under rasemik until the early 1990s.
Rasemik mixture means a mixture containing a pair of enantiomers in equal amounts. So how do I obtain an enantiomer with enantiomeric excess (EE) is high? Enantiomeric excess means that the configured percentage of the R enantiomer reduced the percentage of spouses who berkonfigurasi S enantiomer in a mixture or vice versa. Before answering that question, keep in mind two basic principles of optical isomers, namely:
A pair of enantiomers having the physical properties (boiling point, solubility, etc.) are similar but differ in the direction of rotation of the polarimeter and interaction with other chiral substances.
A pair of diastereoisomers having the physical properties and the rotation angle polarimeter which differ from each other. In fact often the reaction takes a different way. This means that we can separate a mixture of two diastereoisomers by means of physics (distillation, crystallization, etc.). But can not separate a mixture of two enantiomers by means of physics, for a pair of enantiomers have the same physical properties. In conclusion, we can easily separate a mixture of two diastereoisomers, but it will be difficult to separate a mixture of two enantiomers.
Then how to obtain an enantiomer with high ee? Louis Pasteur is said never to separate the two enantiomers of tartaric Sodium Amoium using tweezers. This can happen because the two enantiomers crystallize separately. This method is often referred to the resolution. This is less effective because not all enantiomers crystallize separately.
So the resolution can not be regarded as a common technique. Another way that is often taken by the chemists is a biochemical route by using enzymes or microorganisms to produce the pure enantiomer. For example, (R)-Nikotina can be obtained by incubating the mixture rasemik (R)-Nikotina and (S)-Nikotina in a container of the bacteria Pseudomonas putida. The bacteria will only oxidize (S)-Nikotina, whereas (R)-Nikotina will remain in the container. Some other products of the biochemical route is Monosodium L-glutamate, L-Lysine and L-Menthol. Nomenclature system of D and L is called the relative configuration. This system is often used in naming the amino acids and carbohydrates.
Unfortunately not all of enantiomers can be produced with high ee through this biochemical route. This is because the specificities of the enzymes and microorganisms. For example, the bacteria Pseudomonas putida can not be used to separate the (+)-Menthol with (-)-Menthol.
The organic chemists such as Ryoji Noyori and William S. Knowles did not lose the sense in solving this problem. William S. Knowles managed to synthesize a compound called (R, R)-DiPAMP (Fig. 2.). It uses the (R, R)-DiPAMP as a ligand to form complex compounds with Rh metal. These complex compounds are very useful in asymmetric hydrogenation processes enamida group. With this complex compound, he managed to synthesize L-DOPA which is very useful in the treatment of Parkinson's disease with a purity of 95 percent ee.
In addition to L-DOPA, the complex compound is also often used to synthesize the acid? alpha-amino acids with high ee, L-Phenilalanin example, L-tryptophan, L-Alanine, L-lysine, etc., except for aspartic acid because it has two adjacent carboxylate groups.
On the other hand, Ryoji Noyori synthesize compounds that are named BINAP (Figure 3.). He used BINAP as a ligand to form complex compounds with metal Ru. These complex compounds are very flexible, because it can be used for asymmetric hydrogenation of alkenes, and enantioselective reduction of ketones are. Actually, the enantioselective reduction of ketones is not new, but the use of transition metals as catalysts for the reduction of ketones is usually difficult and is not enantioselective. Enantioselective means a reaction that produces two enantiomers, in which one enantiomer is produced in greater numbers than the enantiomer partner.
Especially for the reduction of ketones, Ryoji Noyori synthesize (S)-BINAP / (S)-diamine Ru (II) catalyst. With these complex compounds are widely produced chiral drugs with low production costs and high purity. For example, L-DOPS, Levofloxacin, Neobenodine, Fosfomycin, fluoxetine hydrochloride, naproxen, and others. For the record L-DOPS is a precursor of Norepinephrine. Norepinephrine is a neurotransmitter to send signals to the heart and blood vessels.
Both of these discoveries have opened new horizons in science and technology. According to reports, until 2000, sales of chiral drugs in enantiomerically pure form in the world has reached 123 billion U.S. dollars. It is also possible the realization of new discoveries, it is even possible that the Indonesian people will make new breakthroughs. Remember, this story is not over, because science is never dead. Finally, science continues to advance Indonesia.
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