本文针对硼中子俘获治疗（BNCT）的第二代临床硼药4-硼酸-L-苯丙氨酸（L-BPA）高效合成难题,设计了新型硼化策略：以L-苯丙氨酸衍生物为原料,CuI为催化剂、NaH作碱,在温和条件下与频哪醇硼烷（HBpin）偶联。该反应可制备医药级高纯度 L-BPA（纯度 > 99.5%）,维持氨基酸L-构型的高对映体过量（ee）>99%;有效解决传统工艺同位素利用度低、手性丢失及低产率难题,且同步提升硼利用效率,大幅降低合成物料成本。本研究有望推动L-BPA 临床应用及BNCT技术临床转化。
李伟豪
,
胡子龙
,
阮兴杰
,
侯薇薇
,
钮玉辉
,
王盛
,
胡明友
. BNCT二代硼药4-硼酸-L-苯丙氨酸（L-BPA）的合成工艺优化[J]. 有机化学, 0
: 202507005
.
DOI: 10.6023/cjoc202507005
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.
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