Held Charles B, Robbins David K
Chemical Process Research & Development, Lilly Research Laboratories, a Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
J Chromatogr Sci. 2003 Sep;41(8):422-7. doi: 10.1093/chromsci/41.8.422.
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.
隐藻素是作为潜在抗癌剂进行研究的大环内酯类化合物。这些大的环状分子是通过一个汇聚过程生成的，该过程利用了几个单独合成的较小片段的偶联。在β-氨基酸片段C的早期合成开发过程中，需要分析方法来表征所研究的各种路线产生的产物。正在评估的一条路线会产生β-(α-甲基苄基)氨基异丁酸的(RR)和(RS)非对映异构体作为中间体。为了测量非对映体过量(%de)，探索了使用高效液相色谱(HPLC)和毛细管气相色谱(GC)技术的分析条件。研究了使用三氟乙酰基和硅烷基衍生物的衍生化方法用于毛细管GC。发现GC研究的结果仅部分成功。确定离子对HPLC是最佳技术，使用戊烷磺酸作为β-(α-甲基苄基)氨基异丁酸胺基的抗衡离子。
