N-((N-⁴-(benzyloxycarbonyl)cytosin-1-yl)acetyl)-N-(2-Boc-aminoethyl)glycine | 144564-94-3

• 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
• 英文名称: N-((N-⁴-(benzyloxycarbonyl)cytosin-1-yl)acetyl)-N-(2-Boc-aminoethyl)glycine
• 英文别名: Boc-Aeg(C[z])-OH；Boc-PNA-C(Z)-OH；2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl-[2-[2-oxo-4-(phenylmethoxycarbonylamino)pyrimidin-1-yl]acetyl]amino]acetic acid
• CAS: 144564-94-3
• 化学式: C₂₃H₂₉N₅O₈
• 分子量: 503.512
• InChiKey: UCPRPVFFEVZHEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  167
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-((N-⁴-(benzyloxycarbonyl)cytosin-1-yl)acetyl)-N-(2-Boc-aminoethyl)glycine 在 四丁基溴化铵 、 碳酸氢钠 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 为溶剂， 反应 15.5h， 生成 (E)-17-[N-(2-(tert-Butyloxycarbonylamino)ethyl)]-N-[N⁴-(benzyloxycarbonyl)cytosine-1-ylacetyl]glycinyloxy-4,7,10,13-tetraoxa-15-heptadecenoic acic
  参考文献：
  名称：

  用于在溶液中和固相上将荧光报告基团连接至肽核酸的聚合策略。

  摘要：

  肽核酸（PNA）与荧光报告基团的位点选择性缀合对于构建可报告特定DNA序列存在的杂交探针至关重要。本文介绍了收敛方法，用于固相合成多标记的PNA低聚物。受保护的PNA的固相合成使得荧光标记能够选择性地附着在C末端（DNA中的3'），这表明进一步操作受保护的PNA片段是可行的。为了与内部位点缀合，引入了一种方法，该方法允许在树脂上组装改性单体，从而无需在溶液中合成整个单体。此外，结果表明，将高度正交的保护基策略与化学选择性缀合反应结合使用，可以快速，自动地进行固相合成双标记PNA探针。通过利用适当附加的荧光团之间的荧光共振能量转移（FRET），可以实时测量核酸杂交。与基于DNA的分子信标类似，双重标记的PNA探针仅在单链状态下发出弱荧光。然而，与互补寡核苷酸的杂交诱导了结构重组并赋予了生动的荧光增强。通过利用适当附加的荧光团之间的荧光共振能量转移（FRET），可以实时测量核酸杂交。类似于基于

  DOI：

  10.1002/1521-3765(20010917)7:18<3911::aid-chem3911>3.0.co;2-1
• 作为产物：
  描述：

  ethyl N-((N-⁴-(benzyloxycarbonyl)cytosin-1-yl)acetyl)-N-(2-Boc-aminoethyl)glycinate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以69%的产率得到N-((N-⁴-(benzyloxycarbonyl)cytosin-1-yl)acetyl)-N-(2-Boc-aminoethyl)glycine
  参考文献：
  名称：

  Synthesis of Peptide Nucleic Acid Monomers Containing the Four Natural Nucleobases: Thymine, Cytosine, Adenine, and Guanine and Their Oligomerization

  摘要：

  The preparation of mixed-sequence PNAs (PNAs containing the four natural nucleobases; thymine, cytosine, adenine, and guanine) is described. The PNA monomers containing thymine, Cbz-protected cytosine, or adenine or benzyl-protected guanine were prepared via convergent syntheses. Subsequent to introduction of the carboxymethyl linker at N-1 of the pyrimidines or N-9 of the purines and suitable protection of exocyclic groups, the nucleobase derivatives were coupled to the Boc-protected backbone esters 10a or 10b and finally hydrolyzed affording the monomers 12a-d. The exocyclic amino groups of cytosine and adenine were protected with a benzyloxycarbonyl group. The exocyclic amino group of guanine was left unprotected whereas O-6 was protected as the benzyl ether. Two mixed-sequence 10-mers, each with five purines incorporated, and a mixed-sequence 15-mer Containing seven purines were assembled essentially following standard solid phase peptide synthesis protocols.

  DOI：

  10.1021/jo00098a042

文献信息

• Nucleic Acid Templated Reactions: Consequences of Probe Reactivity and Readout Strategy for Amplified Signaling and Sequence Selectivity
  作者：Tom N. Grossmann、Oliver Seitz

  DOI：10.1002/chem.200900025

  日期：2009.7.6

  Making the right signals: Reactions in which the DNA target acts as a catalyst allow amplified signaling in the detection of DNA. The reactivity of the peptide nucleic acid (PNA) probes determines whether a given probe set provides high sensitivity or high selectivity. The careful adjustment of reactivity, probe affinity, and the use of a product‐selective readout method allows improvements in the

  发出正确的信号：以DNA靶为催化剂的反应可以在DNA检测中放大信号。肽核酸（PNA）探针的反应性决定了给定的探针组是提供高灵敏度还是高选择性。仔细调整反应性，探针亲和力，并使用产物选择性读出方法，可以改善对DNA单碱基突变的灵敏分析，而几乎没有背景干扰。
• Improved Large-Scale Liquid-Phase Synthesis and High-Temperature NMR Characterization of Short ­(F-)PNAs
  作者：Tobias A. Plöger、Günter von Kiedrowski

  DOI：10.1002/hlca.201100243

  日期：2011.11

  unpaired PNA n‐mers exist in a mixture of 2n conformers undergoing slow exchange and leading to complicated NMR spectra. Structure analysis was improved by recording 1H‐ and 13C‐NMR spectra at elevated temperatures above the coalescence point. Fully protected backbone derivatives show sharp resonances where expected, and spectra of protected PNAs are remarkably simplified, thereby allowing an interpretation

  我们报告了F-PNA三聚体10和PNA三聚体11的大规模合成。关键的改进是（2,4-二氟-5-甲基苯基）乙酸的简便两步合成（2）。相应的F-PNA低聚物10的水溶性是通过合成溶解度增强剂5a来实现的，该增强剂具有两个带正电且仅由PNA固有的结构元素组成。受保护且未配对的PNA n单体存在于2 n个构象异构体的混合物中，它们经历缓慢交换并导致复杂的NMR光谱。通过记录1 H-和13改进了结构分析高于聚结点的高温下的C-NMR谱图。完全受保护的主链衍生物在预期的地方显示出剧烈的共振，并且受保护的PNA的光谱显着简化，从而首次得以解释。修剪器10和11都被视为基于PNA的自我复制系统的构建块。
• A novel synthetic method of peptide nucleic acid ( <scp>PNA</scp> ) oligomers using Boc/ <scp>Cbz‐protected PNA</scp> trimer blocks in the solution phase
  作者：Alagarsamy Periyalagan、In Seok Hong

  DOI：10.1002/bkcs.12513

  日期：2022.5

  production should be easy. However, in the traditional solid-phase synthesis method, the generation of n − 1 or n − 2 deleted oligomers cannot be completely excluded, and purification of crude oligomers is difficult because the target and impurities overlap. Also, for these reasons, scale-up is also limited. Here, we report the efficient synthesis of PNA oligomers in the solid phase using fully protected PNA

  为了将肽核酸 (PNA) 寡聚体用于治疗目的，高纯度水平是必不可少的，特别是大规模生产应该很容易。然而，在传统的固相合成方法中，生成n  - 1 或n − 2 个缺失的寡聚体不能完全排除，粗寡聚体的纯化很困难，因为目标和杂质重叠。此外，由于这些原因，放大也受到限制。在这里，我们报告了使用完全保护的 PNA 三聚体而不是单体在固相中有效合成 PNA 寡聚体。在溶液阶段通过两种不同的途径成功合成了完全受保护的 PNA 三聚体块。当使用三聚体嵌段作为单体在固相中合成 PNA 低聚物时，与使用单体合成低聚物时相比，可以合成更高纯度水平的 PNA。使用此方法时，n  - 1 或n − 不能系统地生产 2 个截断的产品。此外，即使对于含有富含嘌呤和/或 γ PNA 的序列，三聚体块偶联方法也是成功的，这些序列很难通过传统的固相肽合成方法合成。最后，在溶液相中完全合成了两种六聚体和一种十二聚体的PNA寡
• Use of the Dithiasuccinoyl (Dts) Amino Protecting Group for Solid-Phase Synthesis of Protected Peptide Nucleic Acid (PNA) Oligomers^1-3
  作者：Marta Planas、Eduard Bardají、Knud J. Jensen、George Barany

  DOI：10.1021/jo9824394

  日期：1999.10.1

  "Peptide nucleic acid" (PNA) oligomers replace the oligonucleotide backbone of DNA with an achiral and neutral poly[N-(2-aminoethyl)glycine] backbone, and the four-natural nucleobases are attached through methylene carbonyl linkages to the glycine nitrogens. The present work describes the efficient conversion of N-omega-Boc/side-chain Z-protected PNA monomers to the corresponding derivatives protected by the thiolyzable N-omega-dithiasuccinoyl (Dts) function. After acidolytic removal of Boc, treatment with bis(ethoxythiocarbonyl) sulfide gave the N-omega-ethoxythiocarbonyl (Etc) derivatives, which were silylated at the alpha-carboxyl and converted to the heterocycle by reaction with (chlorocarbonyl)sulfenyl chloride. Net yields of homogeneous monomers were 71-78%. Conditions in the solid-phase mode for thiolytic removal of the Dts group, and for coupling of protected monomers, have been studied extensively and optimized. A protocol featuring (i); Dts removal with dithiothreitol (DTT) (0.5 M) in acetic acid (HOAc) (0.5 M)-CH2Cl2 (2 + 8 min) (ii) short neutralization with N,N-diisopropylethylamine (DIEA)-CH2Cl2 (1:19, 1 + 2 min); and (iii) coupling mediated by HBTU-DIEA (3:1) in N-methyl-2-pyrrolidinone (NMP) (3 h) pas applied to the solid-phase synthesis of Dts-T-4-Gly-NH2, Dts-G(Z)-G(Z)-T-A(Z)-Gly-NH2, Dts-A(Z)-T-C(Z)-G(Z)-Gly-NH2, and Dts-G(Z)-C (Z)-A(Z)-T-Gly-NH2. The indicated protected PNA derivatives were released from the support, and their structures were verified by mass spectrometry.

  "肽核酸"(PNA)寡聚体将DNA的寡核苷酸骨架替换为无手性且中性的聚[N-(2-氨基乙基)甘氨酸]骨架，并通过甲基 carbonyl 连接物将四个天然碱基连接到甘氨酸氮上。本研究描述了将N-omega-Boc/侧链Z保护的PNA单体高效转化为相应受硫化N-omega-二硫琥珀酰基(Dts)保护的衍生物。在酸性条件下去除Boc后，使用双(乙氧基 carbonyl)硫化物处理得到N-omega-乙氧基 carbonyl(Etc)衍生物，这些衍生物在 alpha-carboxyl 上被硅化，并与(chlorocarbonyl)sulfenyl chloride反应生成杂环。纯品单体的净收率为71-78%。固相模式下Dts基团的硫醇化去除条件，以及受保护单体的偶联条件，已得到广泛研究和优化。一种包含以下步骤的方案被用于固相合成：(i) 使用二硫苏糖醇(DTT)(0.5 M)在醋酸(HOAc)(0.5 M)-CH2Cl2(2 + 8分钟)中去除Dts；(ii) 使用N,N-二异丙基乙胺(DIEA)-CH2Cl2(1:19, 1 + 2分钟)进行短时间中和；(iii) 使用HBTU-DIEA(3:1)在N-甲基-2-吡咯烷酮(NMP)中进行3小时的偶联。该方案应用于Dts-T-4-Gly-NH2、Dts-G(Z)-G(Z)-T-A(Z)-Gly-NH2、Dts-A(Z)-T-C(Z)-G(Z)-Gly-NH2和Dts-G(Z)-C(Z)-A(Z)-T-Gly-NH2的固相合成。所述受保护的PNA衍生物从载体上分离，并通过质谱法验证了其结构。
• Solid phase synthesis of protected peptide nucleic acids
  作者：Oliver Seitz

  DOI：10.1016/s0040-4039(99)00717-0

  日期：1999.5

  Boc/Z-protected PNA oligomers were synthesised on solid phase. The use of the allylic HYCRON resin allowed for the application of both Boc- and Fmoc-protecting groups. Highest yields were obtained when the monomeric building block was synthesised on solid phase rather than loaded as preformed unit. The selective attachment of fluorescent labels at the C-terminal (3′) end demonstrated for the first

  Boc / Z保护的PNA低聚物是在固相上合成的。烯丙基HYCRON树脂的使用允许同时使用Boc保护基和Fmoc保护基。当单体结构单元在固相上合成而不是作为预制单元加载时，可获得最高的收率。荧光标记在C端（3'）端的选择性附着首次证明了对受保护的PNA片段进行进一步操作是可行的。