To address the challenge of efficient synthesis of 4-borono-L-phenylalanine (L-BPA)—the second-generation clinical boron-containing drug for Boron Neutron Capture Therapy (BNCT)—this study designed a novel borylation strategy. Using an L-phenylalanine derivative as the starting material, CuI as the catalyst, and NaH as the base, a coupling reaction with pinacolborane (HBpin) was achieved under mild conditions. This reaction enables the preparation of pharmaceutical-grade high-purity L-BPA (purity>99.5%) while maintaining a high enantiomeric excess (ee)>99% of the L-configuration of the amino acid. It effectively overcomes the key issues of low isotope utilization, chiral loss, and low yield in traditional processes, while simultaneously improving boron utilization efficiency and significantly reducing raw material costs for synthesis. This study is anticipated to promote the clinical application of L-BPA and the clinical translation of BNCT technology.
Weihao Li
,
Zilong Hu
,
Xingjie Ruan
,
Weiwei Hou
,
Yuhui Niu
,
Sheng Wang
,
Mingyou Hu
. Synthetic Process Optimization for the Second-Generation Boron Drug 4-Borono-L-Phenylalanine (L-BPA) in BNCT[J]. Chinese Journal of Organic Chemistry, 0
: 202507005
.
DOI: 10.6023/cjoc202507005
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