Mirror-image resolution

Scheme 5.3 illustrates the principle of mirror-image resolution, as used by Roques and coworkers [16] in work directed at dual inhibitors of neural en-dopeptidase and ACE. 2-[Acetylthiomethyl]-3-phenylbutanoic acid (3) was... 

Scheme 5.3. Mirror-image resolution of 2-acetylthiomethyl-3-phenylbutanoic acid.

Where unidentate ligands are present, the ability to effect the resolution of an octahedral complex (i.e. to separate 2 optical isomers) is proof that the 2 ligands are cis to each other. Resolution of [PtCl2(en)2] therefore shows it to be cis while of the 2 known geometrical isomers of [CrCl2en(NH3)2] the one which can be resolved must have the cis-cis structure since the trans form would give a superimposable, and therefore identical, mirror image ... 

To understand how this method of resolution works, let s see what happens when a racemic mixture of chiral acids, such as (+)- and (-)-lactic acids, reacts with an achiral amine base, such as methylamine, CH3NH2. Stereochemically, the situation is analogous to what happens when left and right hands (chiral) pick up a ball (achiral). Both left and right hands pick up the ball equally well, and the products—ball in right hand versus ball in left hand—are mirror images. In the same way, both ( H- and (-)-lactic acid react with methylamine equally... 

Suppose that one takes an electron micrograph of such a helical molecule at a resolution sufficient to reveal the helix structure. This micrograph will appear as a projection of the helix in two dimensions (Scheme 19a) and will still not allow one to distinguish between a dextro- and levorotatory helix positioned as mirror images as in Scheme 19a. An unequivocal solution to the problem may be achieved, in analogy to the optical solution illustrated in Section II, if a second micrograph is taken with the plane of the sample tilted in a known direction, yielding a new two-dimensional projection (Scheme 19b). 

Now let us examine the relationships between handedness of Xs, Ca—Ca distance, and X2 values. Among the disulfides for which coordinates were available at 2 A resolution or better (Deisenhofer and Steigemann, 1975 Imoto et al., 1972 Wyckoff et al., 1970 Quiocho and Lipscomb, 1971 Saul et al., 1978 Epp et al., 1975 Huber et al., 1974 Chambers and Stroud, 1979 Hendrickson and Teeter, 1981 Brookhaven Data Bank, 1980 Feldmann, 1977), there are equal numbers with right-handed and left-handed xs- The average Ca—Ca distance across the left-handed ones is 6.1 A, exactly what was seen in the small-molecule structures, but for the right-handed ones the average Ca—Ca distance is 5.2 A. Clearly the two sets of disulfides as they occur in proteins cannot simply be mirror images of one another. 

The observed adsorbate lattice structures show enantiomorphism, that is, adsorption of the right-handed P-heptahehcene (P stands for positive) leads to structures which are mirror images of those observed for M-heptahelicene. This effect can be clearly observed in the high-resolution STM images of Fig. 4.19. Furthermore, the enantiomeric lattices form opposite angles with respect to the [lIO] substrate surface direction. The combined molecule-substrate systems thus exhibit extended... 

A chiral stereoisomer is not superimposable on its mirror image. It does not possess a plane or center of symmetry. The nonsuperimposable mirror images are called enantiomers. A mixture of equal numbers of molecules of each enantiomer is a racemic form (racemate). The conversion of an enantiomer into a racemic form is called racemization. Resolution is the separation of a racemic form into individual enantiomers. Stereomers which are not mirror images are called diastereomers. 

Fig. 2c. It can be seen that at 530 nm, the fluorescence decays mono-exponentially with the fluorescence lifetime of 3.24 ns. The rise of the emission seen below 50 ps in the corresponding FlUp data is obviously not resolved here. In contrast, the TCSP data at 450 nm is described by a triple-exponential decay whose dominant component has a correlation time well below the time resolution. This component is obviously equivalent to the fluorescence decay observed in the FlUp experiment. A minor contribution has a correlation time of about 3.2 ns and reflects again the fluorescence lifetime that was also detected at 530 nm. The most characteristic component at 450 nm however has a time constant of about 300 ps. It is important to emphasize that this 300 ps decay does not have a rising counterpart when emission near the maximum of the stationary fluorescence spectrum is recorded. In other words, the above mentioned mirror image correspondence of the fluorescence dynamics between 450 nm and 530 nm holds only on time scales shorter than 20 ps. Finally, in contrast to picosecond time scales, the anisotropy deduced from the TCSPC data displays a pronounced decay. This decay is reminiscent of the rotational diffusion of the entire protein indicating that the optical chromophore is rigidly embedded in the core of the 6-barrel protein.

Biopolymers in Chiral Chromatography. Biopolymers have had a tremendous impact on the separation of nonsupernnposable. mirror-image isomers known as enantiomers. Enantiomers have identical physical and chemical properties in an achiral environment except that they rotate the plane of polarized light in opposite directions. Thus separation of enantiomers by chromatographic techniques presents special problems. Direct chiral resolution by liquid chromatography (lc) involves diastereomenc interactions between the chiral solute and the chiral stationary phase. Because biopolymers are chiral molecules and can form diastereomeric... 

The crystallization procedure employed by Pasteur for his classical resolution of ( )-tartaric acid (Section 5-1C) has been successful only in a very few cases. This procedure depends on the formation of individual crystals of each enantiomer. Thus if the crystallization of sodium ammonium tartrate is carried out below 27°, the usual racemate salt does not form a mixture of crystals of the (+) and (—) salts forms instead. The two different kinds of crystals, which are related as an object to its mirror image, can be separated manually with the aid of a microscope and subsequently may be converted to the tartaric acid enantiomers by strong acid. A variation on this method of resolution is the seeding of a saturated solution of a racemic mixture with crystals of one pure enantiomer in the hope of causing crystallization of just that one enantiomer, thereby leaving the other in solution. Unfortunately, very few practical resolutions have been achieved in this way. 

Optical resolution did not provide pure enantiomers of 28 in any cases (Table 8) but repeated resolution of the complex forming enantiomeric mixture yielded (IR,2S,5R)-2H in 92-94 % ee. Treatment of the (1S,2R,5>S)-28 containing enantiomeric mixture with the same resolving agent (//.//-isomer of DBTA) did not affect dramatic change of the enantomeric ratio. Pure (lS,2R,5S)-28 could be prepared by the use of the mirror image isomer of DBTA during a repeated resolution (Table 9). 

Zurich 1998, Nobel Prize in Chemistry 1975), he published the first of the many landmarks in stereochemistry that are identified with his name the resolution of Troger s base 1 into its mirror-image components by chromatography on a column of lactose hydrate (44HCA1127). 

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