Enantiomeric discrimination

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]. 

When spread from dilute hexane solution, acid-dependent enantiomeric discrimination was observed in the 11/A compression isotherms of the monolayer at 25°C (Fig. 12). It is interesting to note that at higher subphase acidities, both racemic and enantiomeric film systems become more highly expanded, and the surface pressures where enantiomeric discrimination commences occur at high (85-90 A2/molecule) average molecular areas. This may be taken as direct evidence of headgroup ionization effects. The surface... 

Both the N- (a-methylbenzy 1) stearamide and phospholipid systems as detailed above proved to be difficult systems with which to work. The inability of N- a-methylbenzy 1)stearamide to form stable monolayers or even to spread from the crystal on anything but very acidic subphases presents a significant technical challenge despite the presence of a chiral headgroup that is unobstructed by other molecular features. On the other hand, the phospholipid surfactants that spread to form stable films both from solution and from their bulk crystals on pure water subphases at ambient temperatures displayed no discernible enantiomeric discrimination in any film property. The chiral functionality on these biomolecules is apparently shielded from intermolecular interactions with other chiral centers to the extent... 

Figure 17 shows the 11/A isotherms of racemic and enantiomeric films of the methyl esters of 7V-stearoyl-serine, -alanine, -tryptophan, and -tyrosine on clean water at 25°C. Although there appears to be little difference between the racemic and enantiomeric forms of the alanine surfactants, the N-stearoyl-tyrosine, -serine, and -tryptophan surfactants show clear enantiomeric discrimination in their WjA curves. This chiral molecular recognition is first evidenced in the lift-off areas of the curves for the racemic versus enantiomeric forms of the films (Table 2). As discussed previously, the lift-off area is the average molecular area at which a surface pressure above 0.1 dyn cm -1 is first registered. The packing order differences in these films, and hence their stereochemical differentiation, are apparently maintained throughout the compression/expansion cycles. 

Taken together, the equilibrium spreading pressures of films spread from the bulk surfactant, the dynamic properties of the films spread from solution, the shape of the Ylj A isotherms, the monolayer stability limits, and the dependence of all these properties on temperature indicate that the primary mechanism for enantiomeric discrimination in monolayers of SSME is the onset of a highly condensed phase during compression of the films. This condensed phase transition occurs at lower surface pressures for the R( —)- or S( + )-films than for their racemic mixture. 

N-Stearoyltyrosine. The case of N-stearoylserine methyl ester illustrates temperature-dependent enantiomeric discrimination in both monolayers spread from solution and in equilibrium with the bulk phase. Although the IIIA isotherms suggested large differences in the intermolecular associations in homochiral and heterochiral films of SSME, there exist chiral systems in which enantiomeric discrimination as exhibited in film compression properties is much more subtle. N-Stearoyltyrosine (STy) is such a system. 

Given the strong expression of enantiomeric discrimination in monolayers of JV-stearoylserine methyl ester, the question arises as to whether this discrimination can be maintained in the presence of other, achiral surfactants... 

Enantiomeric discrimination and its relation to film component reorganization upon compression can also be observed in dynamic surface tension hysteresis loops. Figure 26 shows the WjA isotherms generated upon five successive compression/expansion cycles (from II = 0 to lOdyncm-1) of racemic and enantiomeric films containing 17 mole percent palmitic acid. The hysteresis loops, obtained on the apparatus described in Section 2 (p. 63), show that the first compression/expansion cycle of the racemic system is repeated in each successive cycle. Upon expansion of the film from the maximum surface pressure back to Odyncm-1, the racemic film returns to its original state without detectable reorganization of the components. However, the... 

All of the experiments in pure and mixed SSME systems, as well as in the Af-stearoyltyrosine systems, have one common feature, which seems characteristic of chiral molecular recognition in enantiomeric systems and their mixtures enantiomeric discrimination as reflected by monolayer dynamic and equilibrium properties has only been detected when either the racemic or enantiomeric systems have reverted to a tightly packed, presumably quasi-crystalline surface state. Thus far it has not been possible to detect clear enantiomeric discrimination in any fluid or gaseous monolayer state. 

A. Latini, D. Toja, A. Giardini Guidoni, S. Piccirillo, and M. Speranza, Energetics of molecular complexes in a supersonic beam A novel spectroscopic tool for enantiomeric discrimination. Angew. Chem. Int. Ed. 38, 815 817 (1999). 

A. A1 Rabaa, K. LeBarbu, F. Lahmani, and A. Zehnacker Rentien, Van der Waals complexes between chiral molecules in a supersonic jet A new spectroscopic method for enantiomeric discrimination. J. Phys. Chem. A 101, 3273 3278 (1997). 

Figure 15. Comparison of L- and D,L-A-stearoyl-alanine films enantiomeric discrimination is barely discernible. From Zeelen (84).

With regard to the general behavior of oxiranes, studies on kinetic resolution of alkyl or alkoxy substituted linear oxiranes mediated by 0.5 to 0.75 equivalent of HCLA base 53 have shown better enantiomeric discrimination for cis (Table 9, entries 1 and 4) rather than trans or terminal oxiranes (Table 9, entries 2, 3 and 5). 

The determination of enantiomeric excess by MS detection withont chromatographic or electrophoretic separation prior to detection has also grown in interest. The enantiomeric discrimination in the gas phase by MS can be obtained in different ways, for example, by the formation of diastereomeric complexes and from collision-indnced dissociation in the MS/MS mode. For further information abont this topic, see the review by Schng and Lindner [112],... 

Chiral recognition has been achieved by combining central recognition and a fine structure which imposes enantiomeric discrimination. The goal is to allow a diastereomeric host/guest complex to... 

A variety of macrocycles with asymmetric centers have been reported, examples of which are shown in (57) to (66). Chiral discrimination has been observed in the study of thiolysis of activated ester bonds with tetracysteinyl[18]crown-6 (67), e.g. Gly-L-Phe reacts up to 80 times faster than Gly-D-Phe with this ligand.231 The chiral macrocyclic ligand (66) is also capable of enantiomeric discrimination, by assisting in the selective reduction of carbonyl compounds with high optical yields.232,233... 

The isomerization of cyclic allyl alcohols to produce ketones proceeds more cleanly [17]. Effective kinetic resolution of racemic cyclic allylic alcohols has been reported [18]. The isomerization of racemic 4-hydroxy-2-cyclopentanone (29) in the presence of 0.5 mol % of [Rh[(/ )-BlNAP](MeOH)2 + in THF proceeded with 5 1 enantiomeric discrimination at 0°C to give 1,3-cyclopentadione (31) via enol ketone 30, leaving the /(-starting allylic alcohol (91% ee and 27% recovery yield) at 72% conversion after 14 days (eq 3.12). (R)-4-Hydroxy-2-cy-clopentenone is a key building block for prostaglandin synthesis [19]. 

The combination of the high stability, the fast response and good enantiomeric discrimination ability makes MIPs promising materials for chiral chemosensors in the aqueous phase. Further improvement can be expected, as new simple methods for spin-coating were reported recently [31]. 

The protonation constants and the binding constants with different chiral carboxylates have been determined by means of pH-metric titrations. The triprotonated form of (S,S,S,S)-6 showed moderate enantioselectivity with malate and tartrate anions (AAG=0.62 and 0.66 kcal/mol, respectively), the strongest binding being observed in both cases with the L-enantiomer. Good enantiomeric discrimination was obtained with tetraprotonated (R,R)-5 and... 

Speranza [108] has developed a methodology to establish the enantiomeric discrimination of chiral monoalcohols and monoamines by mass spectroscopy. The method is based on the generation of supersonically expanded complexes formed by the alcohol or amine and chromophores as either R-(+)-l-phenyl-etanol or R-(+)-l-phenyl-1-propanol. The complexes thus formed, are ionized by R2PI (resonance 2-photon ionization spectroscopy) and their fragmentation studied by time of flight spectroscopy. It is possible to evaluate the enantiomeric discrimination... 

As discussed in section 3.2, hybrid frameworks provide a unique opportunity to create interesting enantiomerically pure (homochiral), porous networks. One of the motivations for so doing is the possible applications of such networks in the area of chiral separations, which was first demonstrated in 2000 by Rosseinsky and co-workers.83 In more recent work, a homochiral network based upon nickel benzene-1,3,5-tricar-boxylate showed a modest enantiomeric excess (ee) of 8% for the adsorption of a simple naphthol derivative.84 In general, it is found that the enantiomeric discrimination depends upon the relative sizes of the cavities and the sorbate molecules, with better selectivity being found when the size match is close. It also appears that ee values are higher for catalytic applications than chiral separations, as described in the following section. 

To improve the enzyme activities, decreasing the reaction temperature has been reported to enhance the enantiomeric discrimination [46—48]. Lower reaction temperatures were also applied to the lipase-catalyzed resolution of the dynamic cyanohydrin system. At 0 °C, the resolution process required a longer time, but the dynamic system was stable and showed similar intermediate ratios until the reaction was completed. The results (Fig. 6b) indicated that the non-substituted ester products 27B and 27D were preferentially amplified from the dynamic system, especially when the reaction temperature was decreased. Compared to the ratio of the corresponding alcohol intermediates 25A and 25C in the dynamic system, the ratios of the orf/io-substituted esters 27A and 27C were less favored by decreasing the amount of lipase and the reaction temperature. The ratio of the para-substituted ester product 27E did not show any significant enhancement compared to the ratio of its corresponding intermediate 25E. 

By HPLC analysis, the lipase enantiomeric discrimination could be observed from the double dynamic system. The highest enantioselectivity was around 5-10% ee for amides 33A and 36A, respectively. However, when fe/t-butyl methyl ether (TBME), commonly used in lipase-catalyzed reactions, was used as solvent, the lipase enantiomeric discrimination of the dynamic systems was much improved. High enantioselectivities were observed for all three final products 90% ee (33A), 93% ee (36A), and 73% ee (30A). Thus, only three chiral amide products were resolved from dynamic system, containing 24 chiral intermediates, through lipase-... 

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