Enantiomers biological discrimination

As can be seen from Figure 2, the (/ )-enantiomers (eutomers) of the silanols 3 and 7 show a significantly higher affinity for muscarinic M2 and M3 receptors than the corresponding (S)-antipodes (distomers). To the best of our knowledge, this is the first example of a biological discrimination between enantiomeric silicon compounds, with the silicon atom as the center of chirality. The stereoselectivity indices SI [SI = Kn S)/Kd(R) for sila-procyclidine (3) are 1.8 (M2) and 4.1 (M3), respectively. For sila-tricyclamol iodide... 

Biological Discrimination of Enantiomers 189 5-6 Racemic Mixtures 191 5-7 Enantiomeric Excess and Optical Purity 192 5-8 Chirality of Conformationally Mobile Systems 193 5-9 Chiral Compounds without Asymmetric Atoms 195 5-10 Fischer Projections 197... 

Conduritols and inositols are cyclic polyalcohols with significant biological activity. The presence of four stereogenic centers in the stmcture of conduritols allows the existence of 10 stereoisomers. Enzymatic methods have been reported for the resolution of racemic mixtures or the desymmetrization of meso-conduritols. For example, Mucor miehei lipase (MML) showed enantiomeric discrimination between all-(R) and all-(S) stereoisomers ofconduritol E tetraacetate (Figure 6.52). Alcoholysis resulted in the removal of the four acetyl groups ofthe all-(R) enantiomer whereas the all-(S) enantiomer was recovered [141]. 

The biotransformation of organofluorine materials into optically active functionalized fluo-rinated materials along with a discussion on the effect of fluorine atom(s) during enantio-selective and/or diastereoselective transformations is described. The ability of microorganisms to discriminate between enantiomers is particularly important regarding resolution and asymmetric synthesis. Furthermore, the use of chiral fluorinated materials in the design and preparation of new types of biologically active materials is discussed. 

The existence of chirality in nature is of particular importance in numerous recognition processes, often illustrated by examples detectable by non-spectroscopic methods such as the different orange and lemon odors of R-(+)- and S-(-)-limonene, respectively (Fig. 3) [8]. As such, chiral discrimination is also of considerable consequence in the medical sciences, as often one enantiomer is pharmaceutically active whereas the other may show adverse side effects. A historic example is the anti-emetic activity of one of the enantiomers of thalidomide, while the other can cause fetal damage [9,10]. These considerations highlight the importance of chiral discrimination in the production of biologically active materials, whereas on the other hand, the design of routes to asymmetric synthesis presents an active challenge to synthetic chemists worldwide. 

In the abovementioned hydrocarbons, acting as pheromones of certain moth species, the biologically active stereoisomers could be identified because of the bioassays with pure compounds. Nevertheless, the stereoisomeric composition of the natural products remains unknown. Very unfortunately, today there is no way to unambiguously determine the enantiomeric composition of very small amounts of mono- or dimethylalkanes containing more than 10 carbon atoms. Enantioselective GC, usually the method of choice, will not work in these cases, as chiral discrimination of the known stationary phases is too small. As a result, enantiomers will not be separated. 

Furthermore, the chiral discrimination of monoterpenes has been recognized as one of the most important analytical techniques in flavor chemistry and pharmacology because the optically active stereoisomers have different sensory qualities and biological activities. HPLC offers powerful techniques for separation and quantification of enantiomers because of the progressive improvement of chiral chromatographic materials and chiral detectors such as optical rotatory dispersion (ORD) and circular dichroism (CD) detectors. In contrast, determination of chiral compounds by GC typically requires coinjection of the reference compound with known stereochemistry. An HPLC system equipped with a chiral detector, on the other hand, allows direct determination of the configuration of chiral compounds.84... 

From these and many similar examples it became evident that discrimination between enantiomers is often a matter of degree. Absolute discrimination, however, is shown by specific oxidases like D-amino acid oxidase of mammalian kidney and L-amino acid oxidase of snake venom. "No one [member] of this class of biological catalysts has yet been known to attack measurably an amino acid antipodal to its normally susceptible category of substracts ) [Greenstein and Winitz (1961)] [Zellor and Maritz (1945)]. Equally selective is the phosphorylation of mevalonic acid by the enzyme mevalonic kinase the R- form is phosphorylated, the S- form is unaffected (Tchen 1958). 

---