N-甲基-N-叔丁氧羰基-D-苯丙氨酸 | 4530-18-1

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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: N-甲基-N-叔丁氧羰基-D-苯丙氨酸
• 中文别名: Boc-DL-苯丙氨酸
• 英文名称: 2-(tert-butoxycarbonylamino)-3-phenylpropionic acid
• 英文别名: N-tert-butoxycarbonyl-phenylalanine；N-Boc-phenylalanine；2-((tert-butoxycarbonyl)amino)-3-phenylpropanoic acid；N-tert-butoxycarbonyl-DL-phenylalanine；Boc-Phe-OH；BOC-DL-Phenylalanine；2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid
• CAS: 4530-18-1
• 化学式: C₁₄H₁₉NO₄
• mdl: MFCD00558969
• 分子量: 265.309
• InChiKey: ZYJPUMXJBDHSIF-UHFFFAOYSA-N

物化性质

• 熔点：
  106-108 °C
• 沸点：
  426.6±38.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S36/37
• 危险类别码：
  R43
• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储于室温环境。

制备方法与用途

2-(叔丁氧羰基氨基)-3-苯基丙酸是一种苯丙氨酸衍生物[1]。

反应信息

• 作为反应物：
  描述：

  N-甲基-N-叔丁氧羰基-D-苯丙氨酸 在 sodium tetrahydroborate 、 三乙胺 作用下， 生成 N-Boc-DL-苯丙氨醇
  参考文献：
  名称：

  A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [18F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging

  摘要：

  Background: Numerous clinical studies have shown a correlation between increased matrix metalloproteinase (MMP)/a disintegrin and metalloproteinase (ADAM) activity and poor outcome of cancer. Various MMP inhibitors (MMPIs) have been developed for therapeutic purposes in oncology. In addition, molecular imaging of MMP/ADAM levels in vivo would allow the diagnosis of tumors. We selected the dual inhibitor of MMPs and ADAMs, ML5, which is a hydroxamate-based inhibitor with affinities for many MMPs and ADAMs. ML5 was radiolabelled with F-18 and the newly obtained radiolabelled inhibitor was evaluated in vitro and in vivo.Materials and methods: ML5 was radiolabelled by direct acylation with N-succinimidyl-4-[F-18]fluorobenzoate ([F-18]SFB) for PET (positron emission tomography). The resulting radiotracer [F-18]FB-ML5 was evaluated in vitro in human bronchial epithelium 16HBE cells and breast cancer MCF-7 cells. The non-radioactive probe FB-ML5 and native ML5 were tested in a fluorogenic inhibition assay against MMP-2, -9, -12 and ADAM-17. The in vivo kinetics of [F-18]FB-ML5 were examined in a HT1080 tumor-bearing mouse model. Specificity of probe binding was examined by co-injection of 0 or 2.5 mg/kg ML5. Results: ML5 and FB-ML5 showed high affinity for MMP-2, -9, -12 and ADAM-17; indeed IC50 values were respectively 7.4 +/- 2.0, 19.5 +/- 2.8, 2.0 +/- 0.2 and 5.7 +/- 2.2 nM and 12.5 +/- 3.1, 31.5 +/- 13.7, 138.0 +/- 10.9 and 24.7 +/- 2.8 nM. Radiochemical yield of HPLC-purified [F-18]FB-ML5 was 13-16% (corrected for decay). Cellular binding of [F-18]FB-ML5 was reduced by 36.6% and 27.5% in MCF-7 and 16HBE cells, respectively, after co-incubation with 10 mu M of ML5. In microPET scans, HT1080 tumors exhibited a low and homogeneous uptake of the tracer. Tumors of mice injected with [F-18]FB-ML5 showed a SUVmean of 0.145 +/- 0.064 (n = 6) which decreased to 0.041 +/- 0.027 (n = 6) after target blocking (p < 0.05). Ex vivo biodistribution showed a rapid excretion through the kidneys and the liver. Metabolite assays indicated that the parent tracer represented 23.2 +/- 7.3% (n = 2) of total radioactivity in plasma, at 90 min post injection (p.i.).Conclusion: The nanomolar affinity MMP/ADAM inhibitor ML5 was successfully labelled with F-18. [F-18]FB-ML5 demonstrated rather low binding in ADAM-17 overexpressing cell lines. [F-18]FB-ML5 uptake showed significant reduction in the HT1080 tumor in vivo after co-injection of ML5. [F-18]FB-ML5 may be suitable for the visualization/quantification of diseases overexpressing simultaneously MMPs and ADAMs. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.013
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 在 sodium sulfate 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 维生素 C 作用下， 以 甲醇 、 氘代氯仿 、 重水 、 乙腈 、 苯 为溶剂， 反应 25.0h， 生成 N-甲基-N-叔丁氧羰基-D-苯丙氨酸
  参考文献：
  名称：

  Visible Light Photorelease of Carboxylic Acids via Charge-Transfer Excitation of N-Methylpyridinium Iodide Esters

  摘要：

  Iodide contrast sensitization to direct irradiation of charge transfer salts incurs carboxylic acid release via visible light absorption. The photochemical reduction of N-methyl-4-pyridinium iodide esters to release carboxylic acids is examined using H-1 NMR analysis. Photolysis reactions are carried out under mild, biphasic solvent conditions, using a household LED lamp. Carboxylic acid release is reported in high yields, and the viability of this method for synthetic chemistry is demonstrated through a macroscale reaction.

  DOI：

  10.1021/acs.orglett.5b01490

文献信息

• Studies on cardiotonic agents. IV. Synthesis of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying substituted hydantoin and 2-thiohydantoin rings.
  作者：Yuji NOMOTO、Haruki TAKAI、Tadashi HIRATA、Masayuki TERANISHI、Tetsuji OHNO、Kazuhiro KUBO

  DOI：10.1248/cpb.38.3014

  日期：——

  7-dimethoxy-4-quinazolinyl)piperidines carrying substituted hydantoin and 2-thiohydantoin rings was synthesized and examined for cardiotonic activity in anesthetized dogs. Introduction of isopropyl and sec-butyl group at the 5-position of the hydantoin and thiohydantoin rings led to potent inotropic activity. Effects of insertion of an alkyl chain between the piperidine and the hydantoin rings were

  合成了一系列带有取代的乙内酰脲和2-巯基乙内酰脲环的新颖的1-（6,7-二甲氧基-4-喹唑啉基）哌啶，并在麻醉的狗中检查了其强心活性。在乙内酰脲和硫代乙内酰脲环的5-位上引入异丙基和仲丁基导致有效的变力活性。还检查了哌啶和乙内酰脲环之间烷基链插入的影响。研究了该系列中最佳强心活动所需的结构要求。
• The Asymmetric Synthesis of Amines via Nickel-Catalyzed Enantioconvergent Substitution Reactions
  作者：Ze-Peng Yang、Dylan J. Freas、Gregory C. Fu

  DOI：10.1021/jacs.0c13034

  日期：2021.2.24

  dialkyl carbinamines do not provide general access to amines wherein the two alkyl groups are of similar size (e.g., CH2R versus CH2R1). Herein, we report two mild methods for the catalytic enantioconvergent synthesis of protected dialkyl carbinamines, both of which use a chiral nickel catalyst to couple an alkylzinc reagent (1.1–1.2 equiv) with a racemic partner, specifically, an α-phthalimido alkyl chloride

  手性二烷基卡宾胺在有机化学、药物化学和生物化学等领域具有重要意义，例如用作生物活性分子、手性配体和手性催化剂。不幸的是，大多数用于合成二烷基卡宾胺的催化不对称方法不提供获得其中两个烷基具有相似大小的胺的一般途径（例如，CH 2 R与CH 2 R 1 ）。在此，我们报道了两种催化对映异构合成受保护的二烷基卡宾胺的温和方法，这两种方法都使用手性镍催化剂将烷基锌试剂（1.1-1.2当量）与外消旋伙伴偶联，特别是α-邻苯二甲酰亚氨基烷基氯或受保护的 α-氨基酸的N-羟基邻苯二甲酰亚胺 (NHP) 酯。该方法用途广泛，可提供带有一系列官能团的二烷基卡宾胺衍生物。对于NHP酯的偶联，我们进一步描述了一种一锅变体，其中NHP酯原位生成，允许从市售氨基酸衍生物一步生成对映体富集的受保护的二烷基卡宾胺；我们通过将其应用于一系列有趣的目标分子的有效催化对映选择性合成来证明该方法的实用性。
• [EN] DERIVATIVES OF 1-[(CYCLOPENTYL OR 2-PYRROLIDINYL)CARBONYLAMINOMETHYL]-4-(1,3-THIAZOL-5-YL) BENZENE WHICH ARE USEFUL FOR THE TREATMENT OF PROLIFERATIVE, AUTOIMMUNE OR INFLAMMATORY DISEASES<br/>[FR] DÉRIVÉS DE 1-[(CYCLOPENTYL OU 2-PYRROLIDINYL)CARBONYLAMINOMÉTHYL]-4-(1,3-THIAZOL-5-YL)-BENZÈNE QUI SONT UTILES POUR LE TRAITEMENT DE MALADIES PROLIFÉRATIVES, AUTO-IMMUNES OU INFLAMMATOIRES
  申请人：UNIV DUNDEE

  公开号：WO2016146985A1

  公开（公告）日：2016-09-22

  There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, having utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for the preparation thereof, and use in medicine. There is particularly provided PROTACs which bind to a protein within the bromo- and Extra-terminal (BET) family of proteins, and especially to PROTACs including novel small molecule E3 ubiquitin ligase protein binding ligand compounds which selectively induce degradation of the BRD4 protein within the bromodomain of the BET family of proteins.

  提供了新型小分子E3泛素连接酶蛋白结合配体化合物，适用于蛋白质降解靶向嵌合物（PROTACs），以及其制备过程和在医学中的用途。特别提供了能够结合到溴-和额外末端（BET）蛋白家族中的蛋白质的PROTACs，尤其是包括新型小分子E3泛素连接酶蛋白结合配体化合物的PROTACs，其选择性诱导BET蛋白家族中溴结构域内的BRD4蛋白降解。
• ANTIBIOTIC OLIGOPEPTIDES
  申请人：BIOXINESS PHARMACEUTICALS, INC.

  公开号：US20180298053A1

  公开（公告）日：2018-10-18

  Disclosed are methionine mimetics that possess antibiotic properties in prokaryotic cells. These mimetics are coupled to one or more optionally substituted amino acids provided that at least one of the amino acids is phenylglycine, tryptophan, phenylalanine or tyrosine.

  揭示了在原核细胞中具有抗生素特性的蛋氨酸类似物。这些类似物与一个或多个可选择替代的氨基酸偶联，其中至少一个氨基酸是苯基甘氨酸、色氨酸、苯丙氨酸或酪氨酸。
• New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2
  作者：Israa A. Seliem、Adel S. Girgis、Yassmin Moatasim、Ahmed Kandeil、Ahmed Mostafa、Mohamed A. Ali、Mohamed S. Bekheit、Siva S. Panda

  DOI：10.1002/cmdc.202100476

  日期：2021.11.19

  Antiviral drug development for SARS-CoV-2: The design and microwave-assisted synthesis of pyrazine conjugates are reported. Some of the newly synthesized conjugates show better antiviral activity and selectivity indexes than those of the reference drug. All the lead compounds exhibited low cytotoxicity. Thus, these conjugates could lead to the development of potential drug candidates for SARS-CoV-2.

  SARS-CoV-2 抗病毒药物开发：报告了吡嗪缀合物的设计和微波辅助合成。一些新合成的缀合物表现出比参比药物更好的抗病毒活性和选择性指标。所有先导化合物均表现出较低的细胞毒性。因此，这些缀合物可能导致 SARS-CoV-2 潜在候选药物的开发。

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