Exploiting Chirality to Create Generic Counterparts

September 13, 2017

H: The CVS-ian dilemma

More than once, I’ve entered a pharmacy to place an order for a prescription, only to wonder why the hell I was about to pay $60 for twenty tablets when I could get twice by buying the $30 generic version. But is a generic pharmaceutical really the same as its private counterpart? Amazingly, the answer is yes…mostly .

He: The Problem

The biggest issue when creating a generic version of a private drug is making sure that the chemical composition of whatever compound is formed is not identical to that of any competitor’sThis primarily regards pharmaceuticals created in developed countries (especially Western ones). In many developing countries, patent laws are hardly enforced or nonexistent, making this a non-issue. . On first glance, this seems very difficult to accomplish, since generic equivalents have to be made of the same active ingredient(s) as the private version. Luckily, there is a powerful facet of organic chemistry that allows for the accomplishment of such a task. That feature is:

Li: Chirality

Chirality is a hugely important aspect in the understanding and appreciation of molecular structures. Very simply, chirality refers to the asymmetric, non-superimposable relationship between two otherwise identical compounds. This is best understood with an example:

(S)-1-bromoethanol and (R)-1-bromoethanol

S and R refer to the stereochemical geometry at a molecule’s chiral center. It is a convenient way to distinguish stereoisomers. See the CIP priority rules.

It is immediately obvious that these two compounds are the same formulaically1-bromoethanol . But geometrically, they are very different! The two compounds’ hydrogens and bromines are in different spatial configurations, arranged in such a way that the compound on the left can never be superposed onto the one on the right, no matter how much we try to twist or turn it. Any two such compounds are known as stereoisomers - they differ only in their spatial configurations. In this case, the two compounds are a special type of stereoisomer, known as enantiomersStereoisomers of a molecule are enantiomers if they have different configurations at each of their equivalent stereocenters, and if the molecule does not have an internal plane of symmetry. Enantiomers with an internal plane of symmetry are known as meso. Stereoisomers with different configurations at some, but not all, of their equivalent stereocenters are known as diastereomers. .

Here’s where it gets interesting.

See, enantiomers are identical in regards to their physical properties, except in one quality - optical rotation. Each enantiomer rotates polarized light by the same magnitude, but in opposite directions. Thus, enantiomers are different compounds.

This means that one enantiomer can be produced without infringement on the registered sale of another, while providing the same physical propertiesOne enantiomer of a drug will be as medically useful as the other enantiomer, so long as there is no bias among drug receptors. . But there is another problem here, because certain receptors in our bodies only respond to certain enantiomers. In that case, what is a generic equivalent to do?

Be: The Hack

Recall the following fact:

Enantiomers rotate polarized light by the same magnitude, but in opposite directions.

This is the basis for how generic drugs can get away with it. The trick is to mix equal amounts of each enantiomer, creating a racemate - an optically inactiveOptically inactive just means that a mixture or compound does not rotate light - in this case, because the amount and direction of rotation cancels out. mixture of enantiomers. This way, a drug can be made that contains the active ingredient required for its operation, but is different enough in its physical properties and composition from a private counterpart to be competitively acceptable.

So, next time you’re buying medication, save some money with the generic version and a doubled dosage!

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