Synthesis of (<i>R</i>)- and (<i>S</i>)-Fmoc-Protected Diethylene Glycol Gamma PNA Monomers with High Optical Purity
作者:Wei-Che Hsieh、Ashif Y. Shaikh、J. Dinithi R. Perera、Shivaji A. Thadke、Danith H. Ly
DOI:10.1021/acs.joc.8b02714
日期:2019.2.1
synthetic route has been developed for preparing optically pure, Fmoc-protected diethylene glycol-containing (R)- and (S)-γPNA monomers. The strategy involves the application of 9-(4-bromophenyl)-9-fluorenyl as a temporary, safety-catch protecting group for the suppression of epimerization in the O-alkylation and reductive amination steps. The optical purities of the final monomers were determined to be
已经开发了用于制备光学纯的,受Fmoc保护的含二甘醇的(R)-和(S)-γPNA单体的稳健合成路线。该策略涉及应用9-(4-溴苯基)-9-芴基作为临时的,安全的保护基团,用于抑制O-烷基化和还原性胺化步骤中的差向异构化。通过19 F-NMR和HPLC评估,最终单体的光学纯度确定为大于99.5%ee 。新的合成方法非常适合大规模单体生产,大多数合成步骤可提供优异的化学收率,而无需进行简单的后处理和沉淀,而无需进行色谱纯化。