4-10硼酸-L-苯丙氨酸 | 80994-59-8

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 4-10硼酸-L-苯丙氨酸
• 中文别名: 硼[10B]法仑
• 英文名称: 4-(¹⁰B)borono-L-phenylalanine
• 英文别名: L-BPA；L-4‑boronophenylalanine；L-(¹⁰B)BPA；BPA；Boronophenylalanine B-10；(2S)-2-amino-3-(4-(10B)dihydroxy(10B)phenyl)propanoic acid
• CAS: 80994-59-8
• 化学式: C₉H₁₂BNO₄
• 分子量: 208.199
• InChiKey: NFIVJOSXJDORSP-ULMHTEDTSA-N

物化性质

• 熔点：
  285-298 °C (decomp)(Solv: water (7732-18-5))
• 溶解度：
  DMSO：不溶；乙醇：不溶

计算性质

• 辛醇/水分配系数(LogP)：
  -1.68
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  D-果糖 、 4-10硼酸-L-苯丙氨酸 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.08h， 生成 4-dihydroxyboryl-L-phenylalanine-fructose complex
  参考文献：
  名称：

  Clinical implementation of 4-dihydroxyborylphenylalanine synthesised by an asymmetric pathway

  摘要：

  Boron neutron capture therapy (BNCT) is an experimental therapeutic modality combining a boron pharmaceutical with neutron irradiation. 4-Dihydroxyborylphenylalanine (L-BPA) synthesised via the asymmetric pathway by Malan and Morin [Synlett. 167-168 (1996)] was developed to be the boron containing pharmaceutical in the first series of Finnish BNCT clinical trials. The final product was >98.5% chemically pure L-BPA with L-phenylalanine and L-tyrosine as the residual impurities. The solubility of L-BPA was enhanced by complex formation with fructose (BPA-F). The pH and osmolarity of the BPA-F preparation is in the physiological range. Careful attention was given to the pharmaceutical quality of the BPA-F preparations. Prior to starting clinical trials the acute toxicity Of L-BPA was studied in male albino Sprague-Dawley rats. In accordance with earlier studies no adverse effects were observed. After completion of the development work L-BPA solution was administered to brain tumour patients in conjunction with clinical studies for development and testing of BPA-based BNCT. No clinically significant adverse events attributable to the L-BPA i.v. infusions were observed. We conclude that our synthesis development, complementary preclinical and clinical observations justify the safe Use Of L-BPA up to clinical phase III studies with L-BPA produced by the asymmetric pathway, originally presented by Malan and Morin in 1996. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0928-0987(02)00256-7
• 作为产物：
  描述：

  N^α-benzyloxycarbonyl-p-(10B)borono-L-phenylalanine methyl ester 在 盐酸 、 methyloxirane 作用下， 以 异丙醇 为溶剂， 反应 31.0h， 以83.1%的产率得到4-10硼酸-L-苯丙氨酸
  参考文献：
  名称：

  Development of the first and practical method for enantioselective synthesis of 10B-enriched p-borono-l-phenylalanine

  摘要：

  At present p-(B-10)borono-L-phenylalanine (L-(10)Bpa) is used clinically as an excellent B-10 carrier for BNCT; however, its enantioselective synthesis has not been reported yet. The present Letter describes the first and practical method for enantioselective synthesis of B-10-enriched L-Bpa using Z-L-Ser-OMe as the chiral synthon in good total yield and high optical purity. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2008.05.108

文献信息

• 一种4-¹⁰硼酸基-L-苯丙氨酸的制备方法
  申请人：四川瑶天纳米科技有限责任公司

  公开号：CN112574245A

  公开（公告）日：2021-03-30

  本发明公开了一种4‑10硼酸基‑L‑苯丙氨酸的制备方法，包括：采用N‑Boc‑4‑碘‑L‑苯丙氨酸和10硼酸三正丁酯制备中间体N‑Boc‑4‑10硼酸基‑L‑苯丙氨酸；在反应器中加入N‑Boc‑4‑10硼酸基‑L‑苯丙氨酸与丙酮，再加入盐酸溶液，室温搅拌均匀后升温反应，然后蒸馏除去丙酮，剩余反应液温度降至10℃以下，调pH至5.5～6.5，析出白色固体，滤出，使用二氯甲烷打浆洗涤，滤出剩余固体，真空烘干，得到4‑10硼酸基‑L‑苯丙氨酸。本发明通过改变加料顺序的方式，控制反应的速率，使反应对温度的要求变低，在相对温和的低温条件下也能顺利进行，其次降低了正丁基锂和硼酸酯的用量，使反应后处理变得更简单，而且收率较高，大大节省了生产成本，为该产品的工业化提供了可能。
• COMPOUND FOR PREPARING 4-(10B)BORONO-L-PHENYLALANINE
  申请人：Taiwan Biotech Co., Ltd.

  公开号：US20130331599A1

  公开（公告）日：2013-12-12

  Provided is a compound of the following formula (I) for preparing 4-( 10 B)borono-L-phenylalnine: wherein R group represents a protecting group and is selected from the group consisting of: tert-butoxycarbonyl (Boc) group, trityl (Trt) group, 3,5-dimethoxyphenylisopropoxycarbonyl(Ddz) group, 2-(4-Biphenyl)isopropoxycarbonyl (Bpoc) group, and 2-nitrophenylsulfenyl (Nps) group, and the compound has a 10 B purity higher than or equal to 98% and an enantiomeric excess higher than or equal to 99%.

  提供了以下公式（I）的化合物，用于制备4-（10B）硼基-L-苯丙氨酸： 其中R基代表保护基，选自以下组合：叔丁氧羰基（Boc）基团，三苯基（Trt）基团，3,5-二甲氧基苯异丙氧羰基（Ddz）基团，2-（4-联苯基）异丙氧羰基（Bpoc）基团和2-硝基苯基硫基（Nps）基团，该化合物的10B纯度高于或等于98％，对映体过量高于或等于99％。
• METHOD FOR PREPARING L-BPA
  申请人：NEUBORON MEDTECH LTD.

  公开号：US20180155368A1

  公开（公告）日：2018-06-07

  Provided is a method for preparing L-BPA, which includes steps of: reacting N-protected (S)-4-halophenylalanine of Formula I, a boronating agent, Grignard reagent and bis(2-methylaminoethyl)ether to obtain a reaction mixture, wherein the reaction mixture comprises N-protected (S)-4-boronophenylalanine of Formula II and the R 2 group represents a protecting group; isolating the N-protected (S)-4-boronophenylalanine from the reaction mixture; and deprotecting the R 2 group of the N-protected (S)-4-boronophenylalanine to obtain L-BPA, wherein the L-BPA has a structure of Formula III.

  提供了一种制备L-BPA的方法，包括以下步骤：将式I中的N-保护的(S)-4-卤苯丙氨酸、硼化试剂、格氏试剂和双(2-甲基氨基乙基)醚反应，得到反应混合物，其中反应混合物包括式II中的N-保护的(S)-4-硼苯丙氨酸，R2基团代表保护基； 从反应混合物中分离出N-保护的(S)-4-硼苯丙氨酸；去保护N-保护的(S)-4-硼苯丙氨酸的R2基团，得到L-BPA，其中L-BPA具有式III的结构。
• [10B]Pinacolborane을 이용한 [10B]-L-4-boronophenylalanine (LBPA)의 새로운 합성법
  申请人：Gachon University of Industry-Academic cooperation Foundation 가천대학교 산학협력단(220040376324) BRN ▼129-82-07687

  公开号：KR20180060319A

  公开（公告）日：2018-06-07

  본 발명은 새로운 항암 치료 기법인 BNCT (Boron neutron capture therapy, 붕소 중성자 포획 시술)에 이용되는 붕소화합물인 [B]LBPA를 합성하는 방법에 대한 것이다. 더욱 자세하게는, 합성을 위해 중요한 중간체인 [B]pinacolborane의 합성법 및 이를 이용한 [B]LBPA의 합성 방법에 관한 것이다. 상기와 같은 본 발명에 따르면, 정상 세포에 대한 부작용이 최소화 된 새로운 항암 치료 기법인 BNCT의 임상 시험에 사용되는 [B]LBPA를 높은 10B 효율성과 쉬운 합성법으로 대량 생산할 수 있는 효과가 있다.

  本发明涉及一种合成用于新的抗癌治疗技术BNCT（Boron neutron capture therapy，硼中子俘获疗法）的硼化合物[B]LBPA的方法。更具体地说，本发明涉及[B]pinacolborane的合成方法以及利用其合成[B]LBPA的方法。根据本发明，可以高效地生产[B]LBPA，用于BNCT的临床试验，从而最小化对正常细胞的副作用。此外，该方法具有高效的10B效率和易于合成的优点。
• 一种4-二羟
  申请人：重庆波克底科技开发有限责任公司

  公开号：CN115466279A

  公开（公告）日：2022-12-13

  本发明提供一种4‑二羟10硼基‑L‑苯丙氨酸的制备方法，包括如下步骤：S1、10硼酸与正丁醇在催化剂的作用下，通过回流反应得到10硼酸三丁酯；S2、将N‑Boc‑4‑碘‑L‑苯丙氨酸在氮气氛围下，溶于无水四氢呋喃中，搅拌溶解后，滴加Konchel型格氏试剂作用下，然后再滴加10硼酸三丁酯，滴加完毕后升温至室温反应得化合物N‑Boc‑4‑二羟10硼基‑L‑苯丙氨酸；S3、将N‑Boc‑4‑二羟10硼基‑L‑苯丙氨酸溶于丙酮、盐酸中，升温至50℃反应2小时，减压浓缩除去溶剂，滴加稀碱水溶液调pH＝6，析晶，过滤得粗品，粗品再用纯化溶剂进行纯化，然后过滤干燥后得4‑二羟10硼基‑L‑苯丙氨酸。该制备方法反应条件温和，后处理简单，产率高，成本低，且适用于工业化生产。