Chiral molecules discovery

The discoveries of optical activity and enantiomeric structures (see the box, page 97) made it important to develop suitable nomenclature for chiral molecules. Two systems are in common use today the so-called d,l system and the (R,S) system. 

As a result, the CD of a chiral molecule can in principle be used to determine its enantiomeric form, referred to as its Absolute Configuration (AC). Since the discovery of CD by Cotton [1], the determination of the ACs of chiral compounds has been the predominant application of CD spectroscopy. 

How important is chirality Based on the percentage of chiral compounds entering phase I development in the last year, the importance of chirality varies greatly between companies. In one case, all phase I candidates were chiral, in another, just 5%. In the recent past, some discovery groups were deliberately avoiding chiral molecules to circumvent perceived complications. 

From the chirality standpoint the next fundamental development occurred in 1874, when the tetrahedral carbon atom was proposed as a basis for molecular chirality by the Dutch and French chemists Jacobus Henricus van t Hoff (1852— 1911) [47, 48] and Joseph Achille LeBel (1847-1930) [49], respectively, independently and almost simultaneously. The discovery of the asymmetric carbon atom (van t Hoff s terminology) finally provided the explanation for the existence of optical isomers and for the chiral nature of the molecules of optically active substances, including many drugs. In his original 1874 pamphlet proposing the tetrahedron [47] van t Hoff listed camphor as a chiral molecule, but the structure he gave (19) was incorrect. 

Biocatalysts are becoming increasingly important in the production of chiral molecules, pharmaceutical intermediates, and medium to high value chemicals and monomers for biomaterials, from alternative and petrochemical feed stocks (1-4). Discovery and screening of biocatalysts for specific chemical transformations are extremely in rtant component in the development of... 

Spatial inversion has an important position in chemistry as the operation that connects two different enantiomers of a chiral molecule. Biochemically it is observed that for living organisms only L-amino acids are present in proteins, and that DNA and RNA are built up from D-sugars. In the wake of the discovery of P-odd processes, suggestions have been made that there may be a connection between this type of interaction and the natural selection of only one enantiomeric form for biochemical processes. It is possible to envision some interaction between molecular structure and the weak force that would favor one of the enantiomers energetically. 

According to the concept of asymmetric activation, a chiral molecule (activator) is able not only to selectively activate one enantiomer of a racemic chiral catalyst but also to make the enantiopure catalyst even more efficient, that is, to produce a higher enantiomeric excess in the product than can the enantiomerically pure catalyst on its own [3, 11]. On the basis of this concept, Mikami and coworkers [29] have successfully applied the combinatorial approach to the discovery of highly enantioselective catalysts for addition of diethylzinc to aldehydes, via screening of the catalyst diversity generated by a combination of chiral ligand and activator... 

In the early days following the discovery of chirality it was thought that only molecules of the type CWXYZ, multiply substituted methanes, were important in this respect and it was said that a molecule with an asymmetric carbon atom forms enantiomers. Nowadays, this definition is totally inadequate, for two reasons. The first is that the existence of enantiomers is not confined to molecules with a central carbon atom (it is not even confined to organic molecules), and the second is that, knowing what we do about the various possible elements of symmetry, the phrase asymmetric carbon atom has no real meaning. 

This situation changed dramatically in 1996 with the discovery of strong electro-optic (EO) activity in smectics composed of bent-core, bowshaped, or banana-shaped achiral molecules.4 Since then, the banana-phases exhibited by such compounds have been shown to possess a rich supermolecular stereochemistry, with examples of both macroscopic racemates and conglomerates represented. Indeed, the chiral banana phases formed from achiral or racemic compounds represent the first known bulk fluid conglomerates, identified 150 years after the discovery of their organic crystalline counterparts by Pasteur. A brief introduction to LCs as supermolecular self-assemblies, and in particular SmC ferroelectric and SmCA antiferroelectric LCs, followed by a snapshot of the rapidly evolving banana-phase stereochemistry story, is presented here. 

The Diels-Alder reaction is a powerful synthetic process for constructing complex molecules. The reaction has been extensively studied and refined since its discovery in 1928.1 The most attractive feature of the Diels-Alder reaction is its simultaneous, regioselective construction of two bonds, resulting in the creation of up to four chiral centers with largely predictable relative stereochemistry at the bond formation sites. Theoretically, there are a total of 24 = 16 stereoisomers when atoms marked with an asterisk are all chiral centers (Scheme 5-1) therefore, the complete control of the reaction process to obtain enantiomeri-cally pure products has been the object of active research in many laboratories. 

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