Published:Journal of Chromatographic Science,
ISSN 0021-9665Volume
41, Number 8, September 2003, pp. 422-427
Investigation of Liquid and Gas Chromatography Techniques for
Separation of Diastereomers of b-(a-Methylbenzyl) Amino Isobutyric Acid
Charles B. Held and David K. Robbins
Chemical Process Research & Development, Lilly Research Laboratories, a
Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN
46285
Cryptophycins are macrolides investigated as potential
anticancer agents. These large cyclic molecules are generated via a convergent
process, utilizing the coupling of several smaller fragments synthesized individually.
During early synthetic development of the b-amino acid fragment C, analytical
methods are necessary for the characterization of products resulting from the
various routes being studied. One route being evaluated produces (RR) and (RS)
diastereomers of b-(a-methylbenzyl) amino isobutyric acid as intermediates. To
measure diastereomeric excess (%de), assay conditions using high-performance
liquid chromatography (HPLC) and capillary gas chromatographic (GC) techniques
are explored. Derivatization methods using trifluoroacetyl- and silyl-derivatives
are investigated for use with capillary GC. The results of the GC investigations
are found to be only partially successful. Ion-pair HPLC is determined to be
the optimal technique, utilizing pentanesulfonic acid as the counter ion to the
amine group of b-(a-methylbenzyl) amino isobutyric acid.
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