Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
Bioorg Med Chem Lett. 2018 Jun 1;28(10):1915-1918. doi: 10.1016/j.bmcl.2018.03.075. Epub 2018 Mar 28.
p-Boronophenylalanine (l-BPA) is applied in clinical settings as a boron carrier for boron neutron capture therapy (BNCT) to cure malignant melanomas. Structural modification or derivatization of l-BPA, however, to improve its uptake efficiency into tumor cells has scarcely been investigated. We successfully synthesized (S)-2-amino-3-(4-boronophenyl)-2-methylpropanoic acid in enantioenriched form as a novel candidate molecule for BNCT. Key steps to enhance the efficiency of this synthesis were enantioselective alkylation of N-protected alanine tert-butyl ester with a Maruoka catalyst and Miyaura borylation reaction to install the boron functionality.
p-硼苯丙氨酸（l-BPA）在临床环境中作为硼载体用于硼中子俘获治疗（BNCT）以治疗恶性黑色素瘤。然而，为了提高其进入肿瘤细胞的摄取效率，对 l-BPA 的结构修饰或衍生化研究甚少。我们成功地以对映体富集的形式合成了（S）-2-氨基-3-（4-硼苯）-2-甲基丙酸，作为 BNCT 的新型候选分子。提高该合成效率的关键步骤是使用 Maruoka 催化剂对 N-保护的丙氨酸叔丁酯进行对映选择性烷基化，以及进行 Miyaura 硼化反应以安装硼官能团。
