Chiral centers chirality without

Biocatalysis is becoming an established method to assist in the manufacture of synthetic targets and, in particular, chiral tine chemicals.13 The ability of enzymes (whether isolated or within an intact cell) to cause resolution or synthesis of chiral centers is without precedent, and there is consequently a strong drive to implement such processes in industry. 

A stereogenic carbon atom (chiral center, chiral atom, asymmetric atom) is bound to four unlike groups and thus generates chirality. Note that a molecule may possess a molecular chirality without having a stereogenic center. 

A molecule can be chiral without having a chiral center if it has a chiral shape such as a propeller or helix. A molecule is not chiral if it contains an internal mirror plane. A compound can contain chiral centers and not be chiral if there is an internal mirror plane. Whenever you are uncertain, build the model of the compound and try to superimpose it on a model of its mirror image. See the Appendix for how to name chiral compounds. 

Additivity of the various contributions has been demonstrated for many complexes. The contributions are from the chiral configuration of chelate rings (configurational effect), the chiral chelate conformation (conformational effect), and the presence of asymmetric centers in the ligands. As expected, the contributions are considerably greater for asymmetric atoms which are coordinated to the chromophore than for others (see below). The contributions from chiral ring conformations and from asymmetric centers on the ligands often are inseparable. Complexes of 2,2 -diaminobiphenyl (dabp) of the type [Co(dabp) (en)2H+ have been of interest (], 8) since the coordinated non-planar dabp is chiral without an asymmetric center. 

While the answer to this question is uncertain, there have been some interesting developments in this area. It has been shown that life (as it exists today anyway) cannot arise from a racemic mixture of amino acids because the presence of chiral centers in many biomolecules is crucial for biological function. The self-replication of DNA relies on the presence of chiral centers and without a shared chirality, the error rate in DNA replication would cause severe problems for many longer-lived plants and animals. One hypothesis for the origin of chirality is that molecules from outer space reached Earth with a net chirality already present. Another is that the net chirality in amino acids was established on Earth in a very short period of time. It s a pretty interesting thing to think about, and this topic is a subject of ongoing research and debate. 

I.I.3.8. Chirality without Stereocenters Not only does a plane of symmetry, which divides a molecule into two exactly identical halves, guarantee achirality, but there are also other elements of symmetry that will make a molecule with stereogenic centers optically inactive. For example, a center of symmetry, a point at which aU the straight lines joining identical points in the molecule cross each other, will be responsible that such molecules do not show an enantio-merism and therefore are not optically active (Figure 1.21). 

The configuration at the chiral centers C-4a, C-5a, and C-12a determine the conformation of the molecule. In order to retain optimum in vitro and in vivo activity, these centers must retain the natural configuration. The hydrophobic part of the molecule from C-5 to C-9 is open to modification ia many ways without losing antibacterial activity. However, modification at C-9 may be critical because steric iateractions or hydrogen bonding with the oxygen atom at C-10 may be detrimental to the activity. 

The spatial aiiangement of substituents at a chirality center is its absolute configuration. Neither the sign nor the magnitude of rotation by itself can tell us the absolute configuration of a substance. Thus, one of the following structures is (-l-)-2-butanol and the other is (—)-2-butanol, but without additional infonnation we can t tell which is which. 

The high enantioselectivity of the exo product opens up a new and readily accessible route to an enantioselective synthesis of interesting isoquinoline alkaloids (Scheme 6.15) [35]. The tricyclic isoxazolidine exo-15b was obtained from the 1,3-dipolar cydoaddition reaction as the pure exo isomer and with 58% ee [34]. As shown in Scheme 6.15 the exo product from the 1,3-dipolar cydoaddition was converted into 17 in two steps without racemization at the chiral center. In addition to the illustrated synthesis, the 6,7-dimethoxy-derived isoxazolidine exo-15b is a very useful precursor for the synthesis of naturally occurring isoquinoline alkaloids [36-40]. 

In most cases of diastereoselective nucleophilic addition reactions where achiral organometallic reagents are added to chiral carbonyl compounds, the chirulity inducing asymmetric center is in close vicinity to the newly created center and cannot be removed without the loss of chirality of either the inducing center or the newly formed center. This type of reaction is very useful in propagating chirality in a molecule from one center to an adjacent one, or in immolative processes. 

Conversion of the unknown to, or formation of the unknown from, a compound of known configuration without disturbing the chiral center. See the glyceraldehyde-glyceric acid example above (p. 138). Since the chiral... 

Although four is the maximum possible number of isomers when the compound has two chiral centers (chiral compounds without a chiral carbon, or with one chiral carbon and another type of chiral center, also follow the rules described here), some compounds have fewer. When the three groups on one chiral atom are the same as those on the other, one of the isomers (called a meso form) has a plane of symmetry, and hence is optically inactive, even though it has two chiral carbons. Tartaric acid is a typical case. There are only three isomers of tartaric acid a pair of enantiomers and an inactive meso form. For compounds that have two chiral atoms, meso forms are found only where the four groups on one of the chiral atoms are the same as those on the other chiral atom. 

In principle this is the method that gives rise to the strongest support-complex interaction. We have considered in this category all the methods in which the support compensates for at least one of the charges of the complex, usually due to the metal, although without considering the exact nature of the metal-support bond, i.e., purely ionic or polarized covalent. In any case, the only possible covalent bond between support and complex would be estabhshed with the metal center, not with the chiral hgand. 

A9-THC (2.1 in Fig. 2) is the only major psychoactive constituent of C. sativa. It is a pale yellow resinous oil and is sticky at room temperature. A9-THC is hpophihc and poorly soluble in water (3 p,g mL ), with a bitter taste but without smell. Furthermore it is sensitive to light and air [4]. Some more physical and chemical data on A9-THC are fisted in Table 1. Because of its two chiral centers at C-6a and C-lOa, four stereoisomers are known, but only (-)-trans-A9-THC is foimd in the Cannabis plant [5]. The absolute configuration of the... 

Without a means to easily control the chirality of benzylic stereocenter, Pettus group members decided to focus on the development of procedures for the construction of adducts without chiral centers. These researchers found that organomagnesium reagents can be used to both generate and consume the o-QM from the corresponding... 

While it was felt that some of the individual issues above could be addressed using the same synthetic sequence (e.g., alternate catalysts for the reduction step) it seemed unlikely that all the above would be solvable, especially as efforts to replace sodium azide with other nucleophiles had failed. Based on this assessment the team felt it would be necessary to evaluate a fundamentally new approach to taranabant and, in particular, to look for a method for installation of the chiral centers without the intermediacy of an alcohol. 

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