Synthetic Process Optimization for the Second-Generation Boron Drug 4-Borono-L-Phenylalanine (L-BPA) in BNCT

doi:10.6023/cjoc202507005

Chinese Journal of Organic Chemistry Previous Articles Next Articles

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BNCT二代硼药4-硼酸-L-苯丙氨酸（L-BPA）的合成工艺优化

李伟豪^a, 胡子龙^a, 阮兴杰^a, 侯薇薇^a, 钮玉辉^a, 王盛^a,b,*, 胡明友^a,*

^a西安交通大学西安 710049;
^b华硼中子科技（杭州）有限公司杭州 310000

收稿日期:2025-09-10 修回日期:2025-09-27
通讯作者: E-mail: mingyouhu@xjtu.edu.cn

Synthetic Process Optimization for the Second-Generation Boron Drug 4-Borono-L-Phenylalanine (L-BPA) in BNCT

Weihao Li^a, Zilong Hu^a, Xingjie Ruan^a, Weiwei Hou^a, Yuhui Niu^a, Sheng Wang^a,b,*, Mingyou Hu^a,*

^aXi'an Jiaotong University, Xi'an, 710049;
^bHBNCT (Hangzhou) Co., Ltd, Hangzhou, 310000

Received:2025-09-10 Revised:2025-09-27

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Abstract

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.

Key words: Boron neutron capture therapy, Boron-containing drugs, Copper iodide, L-BPA, Borylation

Cite this article

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, doi: 10.6023/cjoc202507005.

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BNCT二代硼药4-硼酸-L-苯丙氨酸（L-BPA）的合成工艺优化

Synthetic Process Optimization for the Second-Generation Boron Drug 4-Borono-L-Phenylalanine (L-BPA) in BNCT

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