Macrocyclic Antibiotics as Chiral Selectors - Chiral Separations by Capillary Electrophoresis - page 125

The use of continuous bed or monolithic columns in CEC can be advantageous
because several problems related to packed capillaries are eliminated. Monolithic
material does not contain frits, generally responsible for bubble formation, has no
limitation for the column's length, and so forth. Just for the briel y mentioned advan-
tages other groups investigated the possibility to use monolithic columns modii ed
with macrocyclic antibiotics for the enantiomeric separation by CEC. Gatschelhofer
et al. [106] separated several glycyl-dipeptides by CEC using monoliths prepared by
ring-opening metathesis polymerization (ROMP) with teicoplanin aglycone. A sol-
gel process was used by Dong et al. [107] to prepare a silica monolithic capillary
with immobilized vancomycin. Good enantioseparation was obtained for eight race-
mic compounds by using both nonaqueous polar organic or aqueous mobile phases.
Column efi ciencies as high as 217,400 N/m were obtained.
Table 5.2 reports a summary of the studies done with CEC using stationary phases
containing macrocyclic antibiotics as chiral selectors.

5.5 “LESS COMMON” USED CHIRAL SELECTORS
IN CAPILLARY ELECTROMIGRATION METHODS
Based on the data reported till now in literature, it is evident that macrocyclic anti-
biotics exhibit very high enantioselectivity toward a large number of compounds due
to many stereogenic centers in their structure. However different separation meth-
ods, experimental conditions, and most of all, new chiral selectors are nevertheless
required to obtain better results for discriminating aged and new chiral drugs.
Actaplanin A ( Mr = 1970.27) is a macrocyclic antibiotic belonging to the family
of ristocetin and ristomycin. An amino sugar and several neutral sugars are bonded
to a peptide group [21]. Nonsteroidal anti-inl ammatory drugs, namely, carprofen,
fenoprofen, l urbiprofen, ketoprofen, indoprofen, and suprofen were resolved into
their enantiomers by CZE using this antibiotic. The chiral resolution of the analytes
was investigated in the pH range 5-7 and in the presence of organic modii ers in the
BGE. All compounds were resolved in their enantiomers using a phosphate buffer at
pH 6 containing 0.5 mM of Actaplanin A and 2- methoxyethanol in the concentration
range 15%-30%.
In 1998 Avoparcin, a new glycopeptide antibiotic, was analyzed by HPLC and two
main structurally related compounds were characterized [114]: α -Avoparcin ( Mr 1909)

and -avoparcin ( Mr 1944). Several asymmetric centers, seven aromatic groups, 16

hydroxyl, one carboxylic, and three amino groups were studied and coni rmed by nuclear
magnetic resonance (NMR) [22]. The macrocyclic antibiotic was studied for the enanti-
oseparation of a large number of compounds by CZE by changing the buffer pH, the
concentration of avoparcin etc. Interesting results were obtained by modifying the con-
tent of organic modii er. The authors analyzed selected racemic compounds, namely,
N -3,5-DNB- p -l uoro-phenylalanine, N -3,5-DNB-leucine, and N -3,5-DNB-methionine.
The presence of low concentrations of organic modii ers (<10% methanol, acetonitrile,
isopropanol) in the BGE containing avoparcin increased the enantioresolution of studied
compounds. This effect was ascribed to the fact that the presence of organic modii er in
the BGE destroyed the aggregation of the antibiotic and therefore increased resolution.

β