Asymmetric Synthesis

The International Union of Pure and Applied Chemistry has described asymmetric synthesis as a kind of chemical compound (IUPAC, 1997). It further refers to it as a chemical reaction (or reaction cycle) whereby one or more novel components of chirality are formed in a substrate molecule that brings about the stereoisomeric (enantiomeric or diastereoisomeric) outputs in unmatched amounts.

It is any chemical reaction that determines the structural symmetry in the molecules of a compound, converting the compound into uneven amounts of compounds that vary in the dissymmetry of their organization at the impacted center.

Reactions of this sort commonly entail compounds by which the symmetrical structural feature is a carbon atom bonded to four other atoms or groups of atoms, of which two are the same.

In this sense, one of the groups which seem to have identical likeness is partially adjusted, in that the output is a combination of two dissymmetric compounds, one of which more potent than the other.

Formation

Reactions of this sort are occasioned from the impact of a lack of symmetry in the reacting system. This, sometimes, comes in form of a dissymmetric nucleus in the molecule, a dissymmetric solvent or catalyst, or circularly polarized light, where the gyration of the electromagnetic fields orbits in either from the left to the right or otherwise.

This reaction could also be referred to as stereoselective and if one of the output forms independently, it is called stereospecific. Usually, when construed in the light of the formation of a certain diastereomer, it becomes the synthesis of a reaction by a specific process. In this case, enantiomers are stereoisomers that have diverse construction at every chiral nucleus. Diastereomers are stereoisomers that differ at one or more chiral centers.

This reaction is also known as Enantioselective synthesis, which is an important method in modern chemistry and is especially sacrosanct in the field of pharmaceuticals, as the different enantiomers or diastereomers of a molecule often have varying biological activity.

Asymmetric synthesis is a functional process to dispense stereoisomeric compounds for pharmaceutical uses as a result of opposite enantiomers of molecules, which are known to have different biological applications. Typically, asymmetric synthesis is made to function by homogenous catalysts for the bulk supply of chiral compounds.

A plethora of the building blocks of most biological systems such as Sugars and Amino acids are created as solely one enantiomer. Because of this, living systems possess an increasing amount of chemical chirality and will, oftentimes, react differently with the various enantiomers of a specific compound. Examples of this insight include:

Flavor: the artificial sweetener aspartame has two enantiomers. L-aspartame tastes sweet whereas D-aspartame is tasteless.

Odor: R –(–)-carvone smells like spearmint whereas S –(+)-carvone smells like caraway.

Drug effectiveness: the antidepressant drug Citalopram is dispensed as a racemic mixture. However, it has been proven that only the ( S )-(+) enantiomer is credited for the drug’s responsive effects.

Drug safety: D-penicillamine is utilized in Chelation therapy and for the treatment of Rheumatoid arthritis while L-penicillamine is inimical as it retains the action of pyridoxine, an essential B vitamin.

Although this reaction is very vital, it can also prove very difficult to attain. Enantiomers inhibit similar enthalpies and entropies and therefore should be produced in even amounts by an undirected process – that would lead to a racemic mixture. Enantioselective synthesis can be attained by applying a chiral feature that allows for the construction of one enantiomer over another through interactions at the transition state. This biasing is known as asymmetric induction and can involve chiral features in the substrate, reagent, catalyst, or environment and works by making the activation energy required to form one enantiomer lower than that of the opposing enantiomer. Enantioselectivity is commonly directed by the relative rates of an enantiodifferentiating sate — the point at which one reactant can become either of two enantiomeric products. The rate constant, k, for a reaction is a performance of the activation energy of the reaction, sometimes called the energy barrier, and is temperature-dependent.

Approaches

Enantioselective catalysis is one of the approaches to this reaction. Generally, they are usually referred to as asymmetric catalysis, which is chiral coordination complexes. Catalysis is productive for a wider range of transformations than any other method of enantioselective synthesis. The catalysts are almost invariably rendered chiral by using chiral ligands (it is also possible to generate chiral-at-metal complexes using simpler achiral ligands, but such species have rarely proven to be useful synthetically).

Most enantioselective catalysts are effective at low substrate/catalyst ratios. Due to their high efficacy, they are often suitable for industrial-scale synthesis, even with expensive catalysts. A versatile example of enantioselective synthesis is asymmetric hydrogenation, which is used to reduce a wide variety of functional groups.

The design of developed catalysts is very much influenced by the development of new classes of ligands. Some of these, which are called ‘privileged ligands’, has been seen to be efficient in a sizeable network of reactions. Some of these include BINOL, Salen, and BOX.

Typically, however, a few catalysts are efficient at more than one type of asymmetric reaction. For example, Noyori asymmetric hydrogenation with BINAP/Ru requires a β-ketone, although another catalyst, BINAP/diamine-Ru, widens the scope to α,β- alkenes, and aromatic chemicals. It is the synthesis of a compound by a method that favors the formation of a specific enantiomer or diastereomer.

The basic principle of asymmetric synthesis is using enantiopure reactant or reagent or catalyst or chiral auxiliary, in a way that uneven quantities of stereoisomers are created. In an equal distribution of living organisms, the chemical reactions are catalyzed by the bio-catalysts. All cellular reactions are mediated and catalyzed by enzymes. Enzyme catalyzed reactions without exception produce only one of the two stereoisomers. Every enzyme has an active site into which the substrate has to enter, bind, and get transformed. The active site of an enzyme is a cavity having amino acid functional groups oriented into it. The active site can discriminate against the two faces of the aprochiral center. Thus an enzyme can discriminate the two enantiomers of a compound.