Chemistry Reference
In-Depth Information
The key compound of the synthetic route of Nicolaou et al. was the triazene-
phenylglycine derivative (Scheme 2-8) used for Cu-mediated C-O-D and D-O-E
ring formation. The first ring closure reaction was the formation of the C-O-D
ring, which was followed by macrolactamization of a preformed AB-biaryl amino
acid to yield the AB/C-O-D ring system. The mixture of atropoisomers obtained
from this step afforded a chromatographic separation. To protect
7
Dpg sensitive
to racemization, the amino acid was masked as an amino alcohol, which was oxi-
dized to the carboxy function at a late stage of the aglycon synthesis.
Both total syntheses of Evans et al. and Nicolaou et al. first perform synthesis of
the AB/C-O-D-ring systems before condensation with the D-O-E ring system. The
Evans et al. route was extended by several synthetic steps by the conversion of the
2-OH-group of
5
Hpg and the conversion of nitro substituents after S
N
Ar into hydro-
gen substituents. Problems developed with the transformation of the C-terminal
amide into the carboxy function during deprotection steps. In contrast, Nicolaou
et al. had to face the relatively moderate atroposelectivities and had to solve the
somewhat obscure conversion of the triazene into a phenolic group. Both syntheses
have been compared and discussed in the literature.
6,7,83
2.7 GLYCOPEPTIDES AS CHIRAL SELECTORS IN
CHROMATOGRAPHY AND CAPILLARY ELECTROPHORESIS
The significance of glycopeptide antibiotics as chiral selectors for enantiomeric
separations is often neglected. Among the glycopeptides, vancomycin and ristocetin
are the most important chiral selectors used for thin-layer chromatography (TLC),
84
high-performance liquid chromatography (HPLC), capillary electrochromatogra-
phy (CEC),
85,86
and capillary electrophoresis (CE).
12,87-89
Armstrong et al. used
for the first time vancomycin as a chiral stationary phase for HPLC.
90
The advan-
tages of glycopeptides compared with amino acids, proteins, and cyclodextrines are
the high stability, the commercial availability, and the broad application range to
various separation problems. The glycopeptides used for HPLC are covalently
bound to the packing material. They have a high stability during column packing,
and unlike proteins, no denaturation occurs. They can be used for normal-phase and
for reversed-phase separations. For separation with CE, glycopeptides are added as
a chiral selector to the running buffer in a concentration of 1-4 mmol. In a repre-
sentative example, vancomycin was used for separations of more than 100 race-
mates of structurally highly diverse compounds.
91
The use of micelles of
vancomycin and sodium dodecylsulfate resulted in enhanced separations of race-
mates and extended the applicability toward neutral analytes.
92,93
The broad applicability of glycopeptides is assumed to be based on the interac-
tions with the analyte of various functional groups being part of the glycopeptide
molecule. These comprise hydrophobic, dipole-dipole-, p-p-, and ionic interac-
tions as well as the formation of hydrogen bonds and steric factors.
94-96
Hydrophi-
lic and ionic groups contribute to a good solubility in buffer systems, whereas the
number of stereocenters apparently plays a role for the quality of the separations
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