Homochiral molecules

The term homochiral was introduced by Kelvin in the 1904 publication of his Baltimore Lecture of 1884 and represented a relationship between molecules (see Mislow10). Molecules are homochiral if they possess the same sense of chirality. For example, the right hands of a group of people are homochiral (or alike). More recently, and unfortunately, homochiral has been used in the sense of enantiomerically pure, i.e. one reads of a homochiral compound , which clearly violates the original definition. Since some journals permit the latter usage, readers should be aware of the potential for confusion. 

To illustrate this, the enzyme hog-kidney acylase hydrolyses the natural enantiomers of A-acylamino acids, regardless of the structure of the 

R group in RCH2N(C0Me)C02H iV-acyl-L-amino acids are thus homochirally related (see Mislow and Bickart11). 

The stereogenic centre is C(2). Priorities of groups attached to the stereogenic centre are F OH CHMe Me. If one looks along the C(2)-Me bond from below the molecule, as drawn, one can see that the sequence of priorities decreases 1 2 3 in an anti-clockwise sense hence the configuration is S. 

Alternatively, rotate 13 clockwise around the C-F bond by 120° this gives 13a, which has the group of lowest priority behind the page. Again the configuration is S. Compound 13 is (S)-2-fluoro-3-methylbutan-2-oi. 

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Since chirality means "handness" it is quite pertinent to talk of homochiral molecules when referring to enantiomerically pure substances. Any natural sugar or amino acid is a homochiral product which belongs to the D or L-series, respectively. 

Homochiral molecules readily available from inexpensive sources are useful synthetic building blocks and chiral auxiliaries. 1,4-01-0-benzyl-L-threitol has been used in construction of homochiral crown ethers that are useful as enzyme model systems. Topologically controlled diastereoselective delivery of the Simmons-Smith reagent for 2-cycloalken-l-one 1,4-d1-0-benzyl-L-threitol ketals was recently reported. ... 

Determination of Absolute Configuration. X-irradiation of a crystal produces a diffraction pattern from which the relative spatial orientation of the atoms that make up the molecule may be determined. If the crystal is made of homochiral molecules, the absolute configuration of the compound may be deduced. 

The chiral discrimination in the self-association of chiral l,3a,4,6a-tetrahydroi-midazo[4,5-d]imidazoles 3 has been studied using density functional theory methods [37], (Scheme 3.20). Clusters from dimers to heptamers have been considered. The heterochiral dimers (RR SS or SS RR) are more stable than the homochiral ones (RR RR or SS SS) with energy differences up to 17.5 kJ mol-1. Besides, in larger clusters, the presence of two adjacent homochiral molecules imposes an energetic penalty when compared to alternated chiral systems (RR SS RR SS...). The differences in interaction energy within the dimers of the different derivatives have been analyzed based on the atomic energy partition carried out within the AIM framework. The mechanism of proton transfer in the homo- and heterochiral dimers shows large transition-state barriers, except in those cases where a third additional molecule is involved in the transfer. The optical rotatory power of several clusters of the parent compound has been calculated and rationalized based on the number of homochiral interactions and the number of monomers of each enantiomer within the complexes. 

If the face discrimination in the asymmetric hydroboration reaction is high then the optical purity of the chiral molecule produced will also be high. Efficient asymmetric hydroboration reactions followed by stereospecific cleavage of the boron-carbon bonds produced have been used in syntheses of several complex homochiral molecules (see Section B2.1). 

The formation of racemic mixtures of homochiral oligopeptides is not confined to racemates undergoing spontaneous segregation into enantiomor-phous domains it can also be extended to racemic 2-D crystallites, provided the reaction pathway takes place preferentially between homochiral molecules related by translation symmetry, as in the case of the thioethylester of N -slearoyl-lysinc (Cis-TE-Lys) [193]. It has been experimentally proven by GIXD that racemic Cis-TE-Lys self-assemble into racemic 2-D crystallites, Fig. 15. Moreover, MALDI-TOF MS analyses of oligopeptide samples obtained from the polycondensation of deuterium enantiolabeled monomers have revealed a clear trend toward enhanced formation of di- to hexa-peptides with homochiral sequences, in agreement with a reaction pathway between homochiral monomer molecules related by translation symmetry [193,195]. 

Maycock, C D. et al. An Application of Quinic Acid to the Synthesis of Cyclic Homochiral Molecules A Common Route to Some Interesting Carbocyclic Nucleoside Precursor. 2.4 1993 [151]... 

Fig. 35 a, b. Crystal structure of the dicopper trefoil knot 852 + a) stereo view of a single molecule (the circles representing the atoms are given in black for oxygen, dotted for nitrogen and crosshatched for copper) b) stereoview of the unit cell. It contains two homochiral molecules, four PFg anions and two benzene molecules... 

Figure 2-47 after Cinquini et al. [75] who painstakingly documented the analogy with the pomaceous model. Only examples of the reverse coupe du roi had been known prior to their work. Thus Anet et al. [76] reported the synthesis of chiral 4-(bromomethyl)-6-(mercaptomethyl)[2.2]metacyclophane. They then showed that two homochiral molecules can be combined to form an achiral dimer as shown in and illustrated by Figure 2-48. 

Jacques has evaluated the compilations published by various authors, and has reported that 70-90% of homochiral enantiomers crystallize in the P2i2i2i or P2i space groups [13]. The most frequently encountered chiral space group, P2i2i2i, is orthorhombic, with the unit cell commonly consisting of four homochiral molecules that are related to each other by three binary screw axes. Practically, all of the other homochiral enantiomers crystallize in the monoclinic P2i space group, which is characterized by a plane of symmetry and a twofold axis. The unit cell generally contains two molecules related by a binary screw axis. 

The term chiralty is broadly used within chemistry and drug development however, the terms chiralty or chiral are not always well understood by the reader. To clarify the matter, we can consider that two main situations exist. In the first case a sample consists of equal numbers of molecules having an opposite sense of chiralty (heterochiral molecules). This sample is said to be chiral but racemic. The second case occurs when a sample is made up of molecules that all have the same sense of chiralty (homochiral molecules). In this case the sample is said to be chiral and non-racemic. 

The close-packing criterion for crystal stability generally yields lower free energies for a structure composed of a racemic assembly over that composed of homochiral molecules. This view has been expressed in the empirical rule of Wallach [14], which states that the combination of two opposite enantiomers to form a racemate is accompanied by a volume contraction. The many exceptions to this rule have been discussed in a systematic manner [15]. The modification to Wallach s rule contributed by Walden [16] is more generally valid it states that if an enantiomer has a lower melting point than its corresponding racemate, then the crystals of the latter will have the higher density. 

Stereochemistry e.g. a sample of (+)-tartaric acid is made up of homochiral molecules (not a clear term and still controversially discussed and used). 

Many of the molecules that constitute living organisms, such as amino acids, enzymes, proteins, and DNA, are chiral and present in only one of the two enantiomeric forms. When small, chiral organic molecules interact with the homochiral molecules of biological... 

A whole series of industrial processes has been developed based on transition metal organometallic catalysts. For example, there is intense activity today in the production of homochiral molecules, in which racemic reagents can be transformed into single pure enantiomers of the product by an asymmetric catalyst. This application is of most significance in the pharmaceutical industry where only one enantiomer of a drug is typically active but the other may even be harmful. Other examples include polymerization of alkenes to give polyethylene and polypropylene, hydrocyanation of butadiene for nylon manufacture, acetic add manufacture from MeOH and CO, and hydrosilylation to produce silicones and related materials. 

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