As you know, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable (not identical).
In some drug families, such as Trimipramine, which is a derivative of 1,4-Benzodiazepines, there are two types of enantiomers.(please see the attached file.)
So are the enantiomers of the drug compounds separated in the final product? How is this separation done? If the separation is not done, will there be a problem for the drug user?
If you have any information on this subject, I would appreciate you for sharing it with me.
You can separate the enantiomers from racemic mixtures by (a) mechanical means (b)by reaction with enzymes, (c) by formation of diastereomers, and (d) by chromatography using chiral column.
At first, Yes it makes a big problem, they have to be separated. Because they may have different biological activities ( one of them may have activity toward specific disease the other against or not....etc). So should be separated, If you know their structures, try to convert to their derivatives, separate them , then reconvert to free isomer. Another way , try using MPLC or Flash Chromatography.
Madhukar Baburao Deshmukh , Faiq H S Hussain I appreciate you for sharing your information.
My understanding is that having a mixture of enantiomers contributes to drug side effects. Usually only one enantiomer has the biological activity that is being sought after. The other enantiomer then causes undesired effects in the body.
Robin Bumbaugh Thank you for sharing your point of view with me.)
Yes, that's why.
But unfortunately, some pharmaceutical companies ignore these side effects and do not separate the enantiomers.
Separating the enantiomers from a racemic mixture is challenging since these compounds have the same physical and chemical properties, including solubilities, reactivity, melting points, etc. In fact there are only two differences between two optical isomers: 1) they rotate light in opposite directions and 2) they interact / react differently with other optical isomers. These differences are sufficient to allow their separation and analysis. One possible way to separate one enantiomer from another is by reacting the enantiomers with a second chiral species. Because the two enantiomers will interact differently, the two diastereoisomers obtained may have sufficiently different solubilities to selectively precipitate one of them, allowing its separation by crystallization and subsequent filtration.
Hermás R Jiménez Thank you for sharing your point of view with me.
The Enantiomer have same Physical and Chemical properties. So its is difficult to separate out by simple method. But we can separate 1) by resolution (Chiral stationary phase) Chiral Column Chromatography.
2) Reacting enantiomer with the separate enantiomerically pure compound and form two different diastereomers with different physiochemical properties, then separation will easy by crystallisation.
Nowadays, the situation is not as bad as it used to be - most (if not all) new chiral drugs are marketed as single enantiomers, even if their other enantio/diastereomers do not show obvious side effects; at least huge efforts and a lot of resources are put into making it possible. Even old drugs, initially developed as racemic mixtures, are sometimes reintroduced in enantiomerically pure form (so called "chiral switch").
Sometimes though, practical considerations need to be taken into account - for example, if particular drug enantiomers are quickly interconverting in the human body, separation of these enantiomers does not make sense. But in this situation, full medicinal profile (efficacy, selectivity, side effects, ADME properties etc) for both enantiomers has to be investigated, which is a real pain for pharmaceutical companies.
Some pharmaceutical companies ignore these side effects and do not separate the enantiomers. This situation is rare. For example racemic ibuprofen. But inactive R isomer is converted active S isomer in the body.
Quote: "Some pharmaceutical companies ignore these side effects ..." - perhaps true, but they can ignore this issue only as long as regulatory bodies allow. FDA, for example, us moving towards more and more tough stance on this.
Vladimir Khlebnikov and Salih Abbood and Halil Hosgoren and Arjun Manal Thanks for your help.
The enantiomers of the drug compounds musn't separated in the final product. It is gold rule: The enantiomers of the drug compounds are separated at early stage.Because isolvents ,reactants amounts are n the drug syntesis.
Halil Hosgoren Thank you. It is a main point that you mentioned.
The enantiomers drug compound can be separated in the final product. For this enantimers should be converted their appropriate diasteromers. Your enantiomers could be converted diastereomers via chiral acidic solving agents
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