Enantiomers interconversion

As g seldom exceeds 0.01, except for some chiral ketones (vide infra), the enantiomeric excess (e.e.) that can be expected is usually below 0.5 %.[14] Large g-values are usually associated with forbidden transitions. Decisive factors for a successful molecular switch based on enantiomer interconversion are ... 

The interconversion of zirconaaziridine enantiomers is slower when there is not a primary or secondary alkyl on the zirconaaziridine carbon and isomerization to an azaallyl hydride is not possible. A mechanism that remains available involves the isomerization of each enantiomer to a planar rf complex (Eq. 43), such as that known to interconvert the enantiomers of aromatic aldehydes [16]. For the chelated zirconaaziridine 2d, high-level density functional theory (DFT) methods and a continuum solvation model have shown that enantiomer interconversion occurs through an rj1-imine intermediate (A) rather than through homolysis (B) or heterolysis (C) of the Zr-C bond [71] (Fig. 13). 

Fig. 14 The racemization and, therefore, enantiomer interconversion of 2b can be monitored directly by CD...

Azaallyl hydrides undergo many reactions as well as enantiomer interconversion. Heating 40a at 70 °C overnight led to the C-H activation product 41, identified by and 13C NMR (Eq. 44) [24]. Similar C-H activations (Eq. 45) have been observed by Andersen [73] and Scott [74]. 

C1 Direct enantiomer interconversions and simultaneous multiple ligand substitutions are excluded. 

Inversion of the tetrahydrothiophen ligands in the complexes [Rh(tht)3X3], where X = Cl, Br, or I, takes place intramolecularly, as does enantiomer interconversion of the semiencapsulated complex of the ligand (44). The barrier to the latter process is 46 kJ mol" (at -55... 

Racemization kinetics from CPL measurements. Experiments concerned with the enantiomer interconversion processes were carried out on the [Eu(TTHA)] compound in neutral aqueous solution (Mondry et al., 1994). It has been demonstrated that the CPL spectrum of this system shows only a very slight temperature dependence from 283 to 353 K,... 

Norton s group has demonstrated that the insertion of chiral C2-symmetric diphenylethylene carbonate into the Zr-C bond of a zirconaaziridine led to the asymmetric synthesis of an amino acid methyl ester after a subsequent treatment with NaOH in methanol. Since the zirconaaziridine enantiomers interconverted, the reaction was a DKR. It was shown that the efficiency of this process was determined by the balance between the rate of enantiomer interconversion and the rate of insertion. A slow addition of the inserting enan-tiopure carbonate was often required to maximise the stereoselectivity of the reaction, allowing a diastereoselectivity of up to 90% de combined with a quantitative yield to be obtained, as shown in Scheme 1.59. 

Structures A and A are nonsuperimposable mirror images of each other Thus although as 1 2 dichloro cyclohexane is chiral it is optically inactive when chair-chair interconversion occurs Such interconver Sion IS rapid at room temperature and converts opti cally active A to a racemic mixture of A and A Because A and A are enantiomers interconvertible by a conformational change they are sometimes re ferred to as conformational enantiomers... 

The same kind of spontaneous racemization oc curs for any as 1 2 disubstituted cyclohexane in which both substituents are the same Because such compounds are chiral it is incorrect to speak of them as meso compounds which are achiral by definition Rapid chair-chair interconversion however converts them to a 1 1 mixture of enantiomers and this mix ture IS optically inactive... 

A chiral axis is present in chiral biaryl derivatives. When bulky groups are located at the ortho positions of each aromatic ring in biphenyl, free rotation about the single bond connecting the two rings is inhibited because of torsional strain associated with twisting rotation about the central single bond. Interconversion of enantiomers is prevented (see Fig. 1.16). 

Each of the following molecules might be resolved into two enantiomers if 1) the molecule s preferred geometry is chiral, and 2) the molecule s enantiomeric forms do not readily interconvert (this interconversion is called configuration inversion ). 

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

The applicant should provide justification for using the racemate. Where the interconversion of the enantiomers in vivo is more rapid than the distribution and elimination rates, then use of the racemate is justified. In cases where there is no such interconversion or it is slow, then differential pharmacological effects and fate of the enantiomers may be apparent. Use of the racemate may also be justified if any toxicity is associated with the pharmacological action and the therapeutic index is the same for both isomers. For preclinical assessment, pharmacodynamic, pharmacokinetic (using enantiospecific analytical methods) and appropriate toxicological studies of the individual enantiomers and the racemate will be needed. Clinical studies on human pharmacodynamics and tolerance, human pharmacokinetics and pharma-cotherapeutics will be required for the racemate and for the enantiomers as appropriate. 

Where the drug studied is a racemate, the pharmacokinetics, including potential interconversion, of the individual enantiomers should be investigated in Phase I clinical studies. Phase I or II data in the target population should indicate whether an achiral assay, or monitoring of only one optical isomer where a fixed ratio is confirmed, will be adequate for pharmacokinetic evaluation. If the racemate has already been marketed and the sponsor wishes to develop the single enantiomer, additional studies should include determination of any conversion to the other isomer and whether there is any difference in pharmacokinetics between the single enantiomer administered alone or as part of the racemate. 

Interconversion of the two enantiomers is possible only if the molecule is removed from the surface and rotated by 180° around an axis parallel to the substrate surface. In the case of PVBA adsorbed on Ag l 11, hydrogen bonding leads to a preference for homochiral double chains based on head-to-tail N—H—O bonds and a C2 axis relating the two strands of the chains. The chirality of the chain can be recognized in the STM images by the stagger of one strand relative to the other that arises from C—H—O bonds, as shown in Figure 1.3 [6],... 

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