title: Investigation of liquid and gas chromatography techniques for separation of diastereomers of beta-(alpha-methylbenzyl) amino isobutyric acid.
abstract: 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 beta-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 beta-(alpha-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 beta-(alpha-methylbenzyl) amino isobutyric acid.
authors.affiliation: Chemical Process Research & Development, Lilly Research Laboratories, a Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Held
authors.forename: David K
authors.initials: DK
authors.lastname: Robbins
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D013237:Stereoisomerism