3-硝基-N-Boc-L-酪氨酸叔丁酯 | 351534-61-7

• 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: 3-硝基-N-Boc-L-酪氨酸叔丁酯
• 英文名称: tert-butyl 2-(Boc-amino)-3-(4-hydroxy-3-nitrophenyl)propanoate
• 英文别名: 3-nitro-N-Boc-L-tyrosine tert-butyl ester；tert-butyl (2S)-3-(4-hydroxy-3-nitrophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 351534-61-7
• 化学式: C₁₈H₂₆N₂O₇
• 分子量: 382.414
• InChiKey: IZWMIVQTVFZQMQ-LBPRGKRZSA-N

物化性质

• 沸点：
  517.7±50.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-硝基-N-Boc-L-酪氨酸叔丁酯 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 1-carboxy-2-(4-((dibenzylphosphoryl)oxy)-3-nitrophenyl)ethan-1-aminium trifluoroacetate
  参考文献：
  名称：

  用于水相容性 SN2 18F-氟化小分子放射性示踪剂的“AquaF”构建模块

  摘要：

  尽管广泛使用亲水结构单元来掺入18 F 并改善示踪剂药代动力学，但在水中实现有效的离去基团介导的亲核18 F-氟化（不包括18 F/ 19 F-交换）仍然是一个艰巨的挑战。在这里，我们提出了一种水相容的 S N 2 离去基团介导的18 F-氟化方法，该方法采用预共轭的“AquaF”（膦酰胺氟化物）构建块。在 19 个紧凑的四配位五价 P(V)–F 候选物中，“AquaF”结构单元表现出优异的水溶性、在水中足够的18 F-氟化能力以及优异的体内代谢特性。从候选离去基团池中鉴定出两个硝基吡啶醇离去基团，可进一步增强前体水溶性，能够在水中以 10 –2 M –1 s –1级反应速率常数进行18 F-氟化（超过18 F/ 19 F-交换）在室温下。随着放能协同 S N 2 18 F-氟化机制的确认，这种18 F-氟化方法实现了~90%的放射化学转化率，并在盐水中达到了 175 ± 40 GBq/μmol（使用

  DOI：

  10.1021/jacs.4c05854
• 作为产物：
  描述：

  Boc-保护氨基酸 在 氧气 、 1,2-二十二酰基-sn-glycero-3-胆碱磷酸 作用下， 生成 3-硝基-N-Boc-L-酪氨酸叔丁酯 、 3,3'-二-N-Boc-L-酪氨酸叔丁酯
  参考文献：
  名称：

  Lipid Peroxyl Radicals Mediate Tyrosine Dimerization and Nitration in Membranes

  摘要：

  Protein tyrosine dimerization and nitration by biologically relevant oxidants usually depend on the intermediate formation of tyrosyl radical ((center dot)Tyr). In the case of tyrosine oxidation in proteins associated with hydrophobic biocompartments, the participation of unsaturated fatty acids in the process must be considered since they typically constitute preferential targets for the initial oxidative attack. Thus, we postulate that lipid-derived radicals mediate the one-electron oxidation of tyrosine to (center dot)Tyr, which can afterward react with another (center dot)Tyr or with nitrogen dioxide ((NO2)-N-center dot) to yield 3,3'-dityrosine or 3-nitrotyrosine within the hydrophobic structure, respectively. To test this hypothesis, we have studied tyrosine oxidation in saturated and unsaturated fatty acid-containing phosphatidylcholine (PC) liposomes with an incorporated hydrophobic tyrosine analogue BTBE (N-t-BOC L-tyrosine tert-butyl ester) and its relationship with lipid peroxidation promoted by three oxidation systems, namely, peroxynitrite, hemin, and 2,2'-azobis (2-amidinopropane) hydrochloride. In all cases, significant tyrosine (BTBE) oxidation was seen in unsaturated PC liposomes, in a way that was largely decreased at low oxygen concentrations. Tyrosine oxidation levels paralleled those of lipid peroxidation (i.e., malondialdehyde and lipid hydroperoxides), lipid-derived radicals and BTBE phenoxyl radicals were simultaneously detected by electron spin resonance spin trapping, supporting an association between the two processes. Indeed, alpha-tocopherol, a known reactant with lipid peroxyl radicals (LOO center dot), inhibited both tyrosine oxidation and lipid peroxidation induced by all three oxidation systems. Moreover, oxidant-stimulated liposomal oxygen consumption was dose dependently inhibited by BTBE but not by its phenylalanine analogue, BPBE (N-t-BOC L-phenylalanine tert-butyl ester), providing direct evidence for the reaction between LOO center dot and the phenol moiety in BTBE, with an estimated second-order rate constant of 4.8 x 10(3) M-1 s(-1). In summary, the data presented herein demonstrate that LOO center dot mediates tyrosine oxidation processes in hydrophobic biocompartments and provide a new mechanistic insight to understand protein oxidation and nitration in lipoproteins and biomembranes.

  DOI：

  10.1021/tx900446r

文献信息

• Lipid Peroxyl Radicals Mediate Tyrosine Dimerization and Nitration in Membranes
  作者：Silvina Bartesaghi、Jorge Wenzel、Madia Trujillo、Marcos López、Joy Joseph、Balaraman Kalyanaraman、Rafael Radi

  DOI：10.1021/tx900446r

  日期：2010.4.19

  Protein tyrosine dimerization and nitration by biologically relevant oxidants usually depend on the intermediate formation of tyrosyl radical ((center dot)Tyr). In the case of tyrosine oxidation in proteins associated with hydrophobic biocompartments, the participation of unsaturated fatty acids in the process must be considered since they typically constitute preferential targets for the initial oxidative attack. Thus, we postulate that lipid-derived radicals mediate the one-electron oxidation of tyrosine to (center dot)Tyr, which can afterward react with another (center dot)Tyr or with nitrogen dioxide ((NO2)-N-center dot) to yield 3,3'-dityrosine or 3-nitrotyrosine within the hydrophobic structure, respectively. To test this hypothesis, we have studied tyrosine oxidation in saturated and unsaturated fatty acid-containing phosphatidylcholine (PC) liposomes with an incorporated hydrophobic tyrosine analogue BTBE (N-t-BOC L-tyrosine tert-butyl ester) and its relationship with lipid peroxidation promoted by three oxidation systems, namely, peroxynitrite, hemin, and 2,2'-azobis (2-amidinopropane) hydrochloride. In all cases, significant tyrosine (BTBE) oxidation was seen in unsaturated PC liposomes, in a way that was largely decreased at low oxygen concentrations. Tyrosine oxidation levels paralleled those of lipid peroxidation (i.e., malondialdehyde and lipid hydroperoxides), lipid-derived radicals and BTBE phenoxyl radicals were simultaneously detected by electron spin resonance spin trapping, supporting an association between the two processes. Indeed, alpha-tocopherol, a known reactant with lipid peroxyl radicals (LOO center dot), inhibited both tyrosine oxidation and lipid peroxidation induced by all three oxidation systems. Moreover, oxidant-stimulated liposomal oxygen consumption was dose dependently inhibited by BTBE but not by its phenylalanine analogue, BPBE (N-t-BOC L-phenylalanine tert-butyl ester), providing direct evidence for the reaction between LOO center dot and the phenol moiety in BTBE, with an estimated second-order rate constant of 4.8 x 10(3) M-1 s(-1). In summary, the data presented herein demonstrate that LOO center dot mediates tyrosine oxidation processes in hydrophobic biocompartments and provide a new mechanistic insight to understand protein oxidation and nitration in lipoproteins and biomembranes.
• 10.1021/jacs.4c05854
  作者：Mou, Zhaobiao、Zhu, Yiwei、Zhang, Lei、Ma, Mengting、Li, Zhongjing、Guo, Yiming、Zheng, Jiamei、Zhao, Zixiao、Zhang, Kaiqiang、Chen, Xiaoyuan、Li, Zijing

  DOI：10.1021/jacs.4c05854

  日期：——

  improve tracer pharmacokinetics, achieving effective leaving group-mediated nucleophilic 18F-fluorination in water (excluding 18F/19F-exchange) remains a formidable challenge. Here, we present a water-compatible SN2 leaving group-mediated 18F-fluorination method employing preconjugated “AquaF” (phosphonamidic fluorides) building blocks. Among 19 compact tetracoordinated pentavalent P(V)–F candidates,

  尽管广泛使用亲水结构单元来掺入18 F 并改善示踪剂药代动力学，但在水中实现有效的离去基团介导的亲核18 F-氟化（不包括18 F/ 19 F-交换）仍然是一个艰巨的挑战。在这里，我们提出了一种水相容的 S N 2 离去基团介导的18 F-氟化方法，该方法采用预共轭的“AquaF”（膦酰胺氟化物）构建块。在 19 个紧凑的四配位五价 P(V)–F 候选物中，“AquaF”结构单元表现出优异的水溶性、在水中足够的18 F-氟化能力以及优异的体内代谢特性。从候选离去基团池中鉴定出两个硝基吡啶醇离去基团，可进一步增强前体水溶性，能够在水中以 10 –2 M –1 s –1级反应速率常数进行18 F-氟化（超过18 F/ 19 F-交换）在室温下。随着放能协同 S N 2 18 F-氟化机制的确认，这种18 F-氟化方法实现了~90%的放射化学转化率，并在盐水中达到了 175 ± 40 GBq/μmol（使用