Amides, enantioseparation

Given the wide utility of biocatalysis in the fine chemical industry, why is there such an in-house reliance on classical methods of enantioseparation In fact, why is biocatalysis not applied more generally as a replacement for atom-inefficient or hazardous reactions that are intensively used in the pharmaceutical industry, such as amidation, reduction and oxidation ... 

In the topologically chiral catenane 79 the succession of amide and sulfonamide units defines sequence information for each macrocycle (Figure 47). Consequently one wheel gives an orientation to space and the other defines the configuration [60 b], Remarkably, the enantioseparation performed by Okamoto and Vogtle et al. by HPLC on chiral column materials resulted in baseline separation with a very large separation factor a = 6.95 [61, 62],... 

Accordingly, the spectrum of applicability of these CSPs can be derived. It appears that cellulose- and amylose-carbamate CSPs are excellent for the enantioseparation of SAs with hydrogen donor and/or acceptor sites (amides, carbamates, sulphonamides, hydroxy groups) as well as aromatic moieties, advantageously in combination with bulky groups close to the interaction sites. Due to the broad range of applicability a more detailed list of resolvable SAs would extend this report. However, further information is available from the application guide [172], from review articles [47,99,1(X), and from recently published enantioseparations (Table 9.4). 

Guo L., Lin S.J., Yang YE, Qi L., Wang M.X., Chen Y, Fast enantioseparation of arylglycine amides by capillary electrophoresis with highly sulfated-P-cyclodextrin as a chiral selector. J. Chromatogr. A,... 

Chen et al. reported the enantioseparation of dansyl amino acids on 100 pm i.d. ligand exchange-chiral monolithic microcolumns. Using continuous beds modified with chiral selectors such as L-phenylalanin-amide, L-alaninamide, L-prolinamide, he achieved efficiencies of 1000 plates per meter. 

Spherical shape and narrow particle size distribution are the two key factors for a good HPLC stationary phase. Very recently, Zhang et al. present a chiral MOF with an average particle size of 5 pm for the HPLC separation of alcohol, ketone, flavone, phenol, base, and amide racemates. Ten racemates were well-separated on a 25-cm long MOF column with excellent selectivity. The stereoselectivity likely resulted from the interaction of the analytes with the inner pore space of MOF, which has the most appropriate size and steric fit. Besides, the dispersion, dipole-dipole, and hydrogen-bonding forces which come from the mobile phase may also play significant roles in chiral separation. These results show that chiral MOFs are practicable for HPLC enantioseparation. 

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