Enantiomers preparation through

The next reaction accomplishes coupling of the building blocks 9 and 10 Fragment 10 is prepared through iterative use of (R)-pina-nediol, the enantiomer of 2. by an addition-functionalization sequence similar to that already presented. The vinylic iodide is prepared with a hikai reaction (see Chapter 13). 

In 2006, Alcantara s group reported the first DKR of different benzoins by using Pseudomonas stutzeri lipase (lipase TL) and Shvo s catalyst in organic solvents, obtaining the corresponding (5)-acylated products with yields of up to 87% and enantioselectivities of >99% ee (Scheme 4.21). In all cases, the particular stereobias of the lipase towards the racemic substrates allowed the production of the opposite enantiomer to that prepared through a different enzymatic methodology. 

Remelli et al. [10] proposed a new chiral selector, L-A-decylhistidine (LNDH), prepared through selective alkylation with 1-iododecane of L-histidine at the pyrrolic nitrogen atom of the heterocyclic ring (see Figure 5.If). As shown in Table 5.3, the copper (II) complex of this chiral selector exhibited a high selectivity toward several enantiomers of aromatic amino acids, while no significant separation was observed for DL-valine, DL-alanine, and DL-leucine enantiomers. With respect to the behavior of aromatic amino acids, the D-enantiomer was the most... 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

Synthetic chiral adsorbents are usually prepared by tethering a chiral molecule to a silica surface. The attachment to the silica is through alkylsiloxy bonds. A study which demonstrates the technique reports the resolution of a number of aromatic compoimds on a 1- to 8-g scale. The adsorbent is a silica that has been derivatized with a chiral reagent. Specifically, hydroxyl groups on the silica surface are covalently boimd to a derivative of f -phenylglycine. A medium-pressure chromatography apparatus is used. The racemic mixture is passed through the column, and, when resolution is successful, the separated enantiomers are isolated as completely resolved fiactions. Scheme 2.5 shows some other examples of chiral stationary phases. 

The corresponding tri- and hexa-fluoroacetylacetonates may be similarly prepared. The stability of the acetylacetonate is such that not only can it be resolved on passage through a column of D-lactose, but the enantiomers retain their integrity on nitration or bromination. 

Sulfoxides without amino or carboxyl groups have also been resolved. Compound 3 was separated into enantiomers via salt formation between the phosphonic acid group and quinine . Separation of these diastereomeric salts was achieved by fractional crystallization from acetone. Upon passage through an acidic ion exchange column, each salt was converted to the free acid 3. Finally, the tetra-ammonium salt of each enantiomer of 3 was methylated with methyl iodide to give sulfoxide 4. The levorotatory enantiomer was shown to be completely optically pure by the use of chiral shift reagents and by comparison with a sample prepared by stereospecific synthesis (see Section II.B.l). The dextrorotatory enantiomer was found to be 70% optically pure. 

This technology was extended to the preparation of chiral capillary columns [ 138 -141 ]. For example, enantioselective columns were prepared using a simple copolymerization of mixtures of O-[2-(methacryloyloxy)ethylcarbamoyl]-10,11-dihydro quinidine, ethylene dimethacrylate, and 2-hydroxyethyl methacrylate in the presence of mixture of cyclohexanol and 1-dodecanol as porogenic solvents. The porous properties of the monolithic columns can easily be controlled through changes in the composition of this binary solvent. Very high column efficiencies of 250,000 plates/m and good selectivities were achieved for the separations of numerous enantiomers [140]. 

As seen in Section 1.3.4.1 (synthesis of lotrafiban), the recycling of an unwanted enantiomer resulting from a kinetic resolution allows theoretical yields of up to 100% to be achieved, but it can also create a bottleneck in a production process. DKR, where a starting material undergoes racemization in situ, either spontaneously or through the action of a second catalyst, offers a more efficient approach. This technique has been applied, particularly in academia, to the preparation of a broad range of chiral building blocks, and a number of recent reviews are available. 

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