Catalytic asymmetric synthesis of α-methyl-p-boronophenylalanine
Catalytic asymmetric synthesis of α-methyl-p-boronophenylalanine
复制标题
催化不对称合成α-甲基-对硼苯丙氨酸
DOI：
10.1016/j.bmcl.2018.03.075
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发表时间：
2018
影响因子：
2.7
通讯作者：
Tetsuhiro Nemoto
中科院分区：
文献类型：
--
作者：
Shingo Harada;Ryota Kajihara;Risa Muramoto;Promsuk Jutabha;Naohiko Anzai;Tetsuhiro Nemoto
对硼苯丙氨酸 (l-BPA) 在临床环境中用作硼中子捕获疗法 (BNCT) 的硼载体，以治疗恶性黑色素瘤。然而，为了提高肿瘤细胞的摄取效率而对l-BPA进行结构修饰或衍生化的研究却很少。我们成功合成了对映体富集形式的 (S)-2-氨基-3-(4-硼苯基)-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，以及安装硼官能团的 Miyaura 硼化反应。
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 ofl-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 ofN-protected alaninetert-butyl ester with a Maruoka catalyst and Miyaura borylation reaction to install the boron functionality.