Antipodes, discrimination

Literally hundreds of aldehydes have so far been tested successfully by enzymatic assay and preparative experiments as a replacement for (18) in rabbit muscle FruA catalyzed aldol additions [16,25], and most of the corresponding aldol products have been isolated and characterized. The rabbit FruA can discriminate racemic dl-(18), its natural substrate, with high preference for the D-antipode, but kinetic enantioselec-tivity for nonionic aldehydes is rather low [84,89]. 

Striking examples of this phenomenon are presented for allyl and homoallyl alcohols in Eqs. (5) to (7). The stereodirection in Eq. (5) is improved by a chiral (+)-binap catalyst and decreased by using the antipodal catalyst [60]. In contrast, in Eq. (6) both antipode catalysts induced almost the same stereodirection, indicating that the effect of catalyst-control is negligible when compared with the directivity exerted by the substrate [59]. In Eq. (7), the sense of asymmetric induction was in-versed by using the antipode catalysts, where the directivity by chiral catalyst overrides the directivity of substrate [52]. In the case of chiral dehydroamino acids, where both double bond and amide coordinate to the metal, the effect of the stereogenic center of the substrate is negligibly small and diastereoface discrimination is unsuccessful with an achiral rhodium catalyst (see Table 21.1, entries 9 and 10) [9]. 

The rabbit FruA discriminates the enantiomers of its natural substrate with a 20 1 preference for D-GA3P (12) over its L-antipode [202], Assistance from anionic binding was revealed by a study on a homologous series of carboxylated 2-hydroxyaldehydes which showed optimum enantioselectivity when the distance of the charged group equaled that of 12 (Scheme 15, Fig. 11) [299], The resolution of racemic substrates is not, however, generally useful since the kinetic enantioselectivity for nonionic aldehydes is rather low [202], 3-Azido substituents (69) can lead to an up to 9-fold preference of enantiomers in kinetically controlled experiments [300] while hydroxyl (70 preference for the... 

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... 

In all examples available, geometrically similar antipodes react preferentially in the case of mono- and di-substituted ethylenes respectively, the three exceptions in Table 5 being due to the fact that substrates with similar geometry have different notations (Fig. 5). No observable kinetic resolution is achieved in the platinum-catalyzed hydroformylation of 3-methyl-1-pentene whereas a slight enantiomer discrimination is observed in the case of 2,4-dimethyl-1-pentene. 

S) can be determined. The imprinted polymers show differences in their sensitivities towards the enantiomers of the analytes (Fig. 12, left), whereas the non-chiral reference polymer shows no difference between the two enantiomers (Fig. 12, right). Therefore, a chiral discrimination by the imprinted polymers is proved this can be described by a separation factor a (Table 1). The separation factor is defined here as the ratio of the sensitivity of the template to the sensitivity of the antipode. 

In any case however, antipodal helices cause countercurrent spectra of the optical rotation, so that the observation of just a single Cotton effect is sufficient to discriminate the antipodes and, in case, enantiomeric solutes. For such an experiment the choice of the infrared spectral range is no longer dictated by the structure period but by the presence of suitable transition moments. The low demand for the chiral solute to be characterized (Korte, 1978) is exemplified by Fig. 4.6-14. In the 20 im wide sample cell an area of 3 mm times 3 mm was filled with approximately 200 pg solution containing circa 0.2 pg of either S-(-) or R-(-i-) Thalidomide (Contergan) in a nematic solvent. In the spectral interval shown, at least three oppositely shaped ACE are found, the pronounced one around 836 cm is related to the 7 (C- H), phenyl-H out-of-plane vibration of the... 

According to Dalgliesh [2], three active positions on the selector must interact simultaneously with the active positions of the enantiomer to reveal differences between optical antipodes. This is a sufficient condition for resolution to occur, but it is not necessary. Chiral discrimination may happen as a result of hydrogen-bonding and steric interactions, making only one attractive force necessary in this type of chromatography. Moreover, the creation of specific chiral cavities in a polymer network (as in molecular imprinting techniques) could make it possible to base enantiomeric separations entirely on steric fit. 

Curiously, certain cyclases, notably (+)-bornyl pyrophosphate cyclase and (-)-endo-fenchol cyclase, are capable of cyclizing, at relatively slow rates, the 3S-linalyl pyrophosphate enantiomer to the respective antipodal products, (-)-bornyl pyrophosphate and (+)-endo-fenchol (74,75). Since both (+)-bornyl pyrophosphate cyclase and (-)-endo-fenchol cyclase produce the designated products in optically pure form from geranyl, neryl and 3R-linalyl pyrophosphate, the antipodal cyclizations of the 3S-linalyl enantiomer are clearly abnormal and indicate the inability to completely discriminate between the similar overall hydrophobic/hydrophilic profiles presented by the linalyl enantiomers in their approach from solution. The anomalous cyclization of the 3S-enantiomer by fenchol cyclase is accompanied by some loss of normal regiochemical control, since aberrant terminations at the acyclic, monocyclic and bicyclic stages of the cationic cyclization cascade are also observed (74). The absolute configurations of these abnormal co-products have yet to be examined. 

D-Fructose- 1,6-diphosphate (FDP) aldolase (E.C. 4.1.2.13) from rabbit muscle, catalyzes the equilibrium condensation of dihydroxyacetone phosphate (1 DHAP) with D-glyceraldehyde 3-phosphate (2 G-3-P) to form d-fructose 1,6-diphosphate (3 FDP Scheme l).42-44 The equilibrium constant for this reaction is K = 104 M-1 in favor of the formation of FDP. The stereoselectivity of the reaction is absolute the configuration of the vicinal diols at C-3 and C-4 is always threo (i.e. d-glycero). Although there is a significant discrimination (20 1) between the antipodes of the natural substrate (i.e. d- and l-G-3-P), this selectivity extends to only a few unnatural substrates.33... 

An enantioselcctive activation of prostereogenic ether substrates is achieved with chiral organoaluminum reagents of type 1, which arc able to discriminate, for example, between the two chairlike transition states 2 A and 2B of the -configurated substrate ether 2. The method is chirally flexible, since both antipodal rearranged products can be synthesized by use of either (R)-l or (S)- 137" 139-653. 

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). 

A huge improvement on the KR is determined by an enhanced reaction setup where the racemization of the substrate is carried out in situ in parallel to its resolution. This means that, while the preferred enantiomer is transformed by the enzyme, the other one does not accumulate but is continuously converted into its antipode, thus fueling the reaction until aU the substrate is consumed. In this case, a quantitative conversion can be reached moreover, the enantiomeric purity of the product is often higher as compared to the simple KR, because the enzyme is continuously exposed to comparable concentrations of both of the two stereoisomers, which is a requirement for the maximum efficiency in their discrimination [2,3]. This improved setup is called dynamic kinetic resolution DKR), and it has become very attractive in recent years [4-9]. 

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