Catalytic Asymmetric Synthesis of α-Methyl-p-Boronophenylalanine

Shingo Harada, Ryota Kajihara, Risa Muramoto, Promsuk Jutabha, Naohiko Anzai, Tetsuhiro Nemoto

Index: 10.1016/j.bmcl.2018.03.075

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Abstract

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.