2',3'-O-isopropylidene-3-(benzyloxymethyl)uridine | 191479-26-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2',3'-O-isopropylidene-3-(benzyloxymethyl)uridine
• 英文别名: 3-(benzyloxymethyl)-1-(2,3-O-isopropylidene-β-D-ribosyl)uracil；3-((benzyloxy)methyl)-1-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)pyrimidine-2,4(1H,3H)-dione；1-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-3-(phenylmethoxymethyl)pyrimidine-2,4-dione
• CAS: 191479-26-2
• 化学式: C₂₀H₂₄N₂O₇
• 分子量: 404.42
• InChiKey: VMOWRDZJUMKRJN-VDHUWJSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.59
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101.15
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-3-(benzyloxymethyl)uridine 在 甲酸 、 palladium on activated charcoal 、 氢气 作用下， 以 水 、 异丙醇 为溶剂， 反应 6.0h， 以99%的产率得到2’,3’邻异亚丙基尿苷
  参考文献：
  名称：

  A reliable Pd-mediated hydrogenolytic deprotection of BOM group of uridine ureido nitrogen

  摘要：

  The benzyloxymethyl (BOM) group has been utilized widely in syntheses of a variety of natural and non-natural products. The BOM group is also one of few choices to protect uridine ureido nitrogen. However, hydrogenolytic cleavage of the BOM group of uridine derivatives has been unreliably performed via heterogeneous conditions using Pd catalysts. One of the undesirable by-products formed by Pd-mediated hydrogenation conditions is the over-reduced product in which the C5-C6 double bond of the uracil moiety was saturated. To date, we have generated a wide range of uridine-containing antibacterial agents, where the BOM group has been utilized in their syntheses. In screening of deprotection conditions of the BOM group of uridine ureido nitrogen under Pd-mediated hydrogenation conditions, we realized that the addition of water to the (PrOH)-Pr-i-based hydrogenation conditions can suppress the formation of over-reduced uridine derivatives and the addition of HCO2H (0.5%) dramatically improve the reaction rate. An optimized hydrogenation condition described here can be applicable to the BOM-deprotections of a wide range of uridine derivatives. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.05.035
• 作为产物：
  描述：

  尿嘧啶核苷 在 硫酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.67h， 生成 2',3'-O-isopropylidene-3-(benzyloxymethyl)uridine
  参考文献：
  名称：

  衣霉素V的全合成

  摘要：

  描述了衣霉素V的全合成。该策略基于衣氨酰尿嘧啶的初始构建，该构建被认为在观察到的生物活性中起重要作用。合成的关键是Mukaiyama aldol反应，然后进行呋喃氧化以构建十一碳烯骨架，氰酸酯的[3,3]σ重排以及高度选择性的海藻糖型糖基化。

  DOI：

  10.1021/acs.orglett.7b03623

文献信息

• Synthesis and Evaluation of Bicyclo[3.1.0]hexane-Based UDP-Galf Analogues as Inhibitors of the Mycobacterial Galactofuranosyltransferase GlfT2
  作者：Todd Lowary、Jing Li

  DOI：10.3390/molecules21081053

  日期：——

  galactofuranosyltransferases, GlfT1 and GlfT2, which are involved in the biosynthesis of mycobacterial galactan. In this paper, a group of UDP-Galf mimics were synthesized via reductive amination of a bicyclo[3.1.0]hexane-based amine by reacting with aromatic, linear, or uridine-containing aldehydes. These compounds were evaluated against GlfT2 using a coupled spectrophotometric assay, and were shown to be

  UDP-呋喃半乳糖 (UDP-Galf) 是参与分枝杆菌半乳聚糖生物合成的双功能呋喃半乳糖转移酶 GlfT1 和 GlfT2 的供体底物。在本文中，一组 UDP-Galf 模拟物是通过双环 [3.1.0] 己烷基胺与芳族、线性或含尿苷醛反应的还原胺化合成的。使用耦合分光光度测定法针对 GlfT2 评估了这些化合物，结果表明它们是该酶的弱抑制剂。
• A search for pyrophosphate mimics for the development of substrates and inhibitors of glycosyltransferases
  作者：Ruo Wang、Darryl H. Steensma、Yoshikazu Takaoka、Joanne W. Yun、Tetsuya Kajimoto、Chi-Huey Wong

  DOI：10.1016/s0968-0896(97)00005-9

  日期：1997.4

  The design and synthesis of several beta-1,4-galactosyltransferase inhibitors are reported. Mimics of the pyrophosphate-Mn2+ complex were the focus of the design. Malonic, tartaric, and monosaccharide moieties were used as replacements of the pyrophosphate moiety, and galactose or azasugars with potent galactosidase inhibitory activity were used as the 'donor' component. Compound 6, in which glucose

  报道了几种β-1，4-半乳糖基转移酶抑制剂的设计和合成。焦磷酸盐-Mn2 +配合物的模拟物是设计的重点。丙二酸，酒石酸和单糖部分被用作焦磷酸盐部分的替代物，而具有有效的半乳糖苷酶抑制活性的半乳糖或氮杂糖被用作“供体”组分。以葡萄糖为焦磷酸盐-Mn2 +复合物模拟物，以半乳糖为“供体”成分的化合物6对转移酶表现出最佳的抑制活性，Ki为119.6 microM。
• Total Synthesis of Caprazamycin A: Practical and Scalable Synthesis of <i>syn</i>-β-Hydroxyamino Acids and Introduction of a Fatty Acid Side Chain to 1,4-Diazepanone
  作者：Hugh Nakamura、Chihiro Tsukano、Takuma Yoshida、Motohiro Yasui、Shinsuke Yokouchi、Yusuke Kobayashi、Masayuki Igarashi、Yoshiji Takemoto

  DOI：10.1021/jacs.9b02220

  日期：2019.5.29

  Diastereoselective aldol reactions of aldehydes 12 and 25-27, derived from uridine, with diethyl isocyanomalonate 13 and phenylcarbamate 21 were investigated using thiourea catalysts 14 or bases to synthesize syn-β-hydroxyamino acid derivatives. The 1,4-diazepanone core of 1 was constructed using a Mitsunobu reaction, and the fatty acid side chain was introduced using a stepwise sequence based on model studies.

  描述了具有代表性的脂核苷类抗生素 caprazamycin A (1) 的首次全合成。使用硫脲催化剂 14 或碱研究衍生自尿苷的醛 12 和 25-27 与异氰基丙二酸二乙酯 13 和氨基甲酸苯酯 21 的非对映选择性羟醛反应，以合成合成 β-羟基氨基酸衍生物。1 的 1,4-二氮杂环酮核心使用光信反应构建，并使用基于模型研究的逐步序列引入脂肪酸侧链。值得注意的是，使用钯黑和甲酸实现了整体脱保护，而无需氢化尿苷单元中的烯烃。
• DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors
  作者：Katsuhiko Mitachi、Rita G. Kansal、Kirk E. Hevener、Cody D. Gillman、Syed M. Hussain、Hyun Gi Yun、Gustavo A. Miranda-Carboni、Evan S. Glazer、William M. Clemons、Michio Kurosu

  DOI：10.1021/acs.jmedchem.0c00545

  日期：2020.10.8

  Capuramycin displays a narrow spectrum of antibacterial activity by targeting bacterial translocase I (MraY). In our program of development of new N-acetylglucosaminephosphotransferase1 (DPAGT1) inhibitors, we have identified that a capuramycin phenoxypiperidinylbenzylamide analogue (CPPB) inhibits DPAGT1 enzyme with an IC50 value of 200 nM. Despite a strong DPAGT1 inhibitory activity, CPPB does not show cytotoxicity against normal cells and a series of cancer cell lines. However, CPPB inhibits migrations of several solid cancers including pancreatic cancers that require high DPAGT1 expression in order for tumor progression. DPAGT1 inhibition by CPPB leads to a reduced expression level of Snail but does not reduce E-cadherin expression level at the IC50 (DPAGT1) concentration. CPPB displays a strong synergistic effect with paclitaxel against growthinhibitory action of a patient-derived pancreatic adenocarcinoma, PD002: paclitaxel (IC50: 1.25 mu M) inhibits growth of PD002 at 0.0024-0.16 mu M in combination with 0.10-2.0 mu M CPPB (IC50: 35 mu M).
• Total Synthesis of (−)-Caprazamycin A
  作者：Hugh Nakamura、Chihiro Tsukano、Motohiro Yasui、Shinsuke Yokouchi、Masayuki Igarashi、Yoshiji Takemoto

  DOI：10.1002/anie.201411954

  日期：2015.3.2

  AbstractCaprazamycin A has significant antibacterial activity against Mycobacterium tuberculosis (TB). The first total synthesis is herein reported and features a) the scalable preparation of the syn‐β‐hydroxy amino acid with a thiourea‐catalyzed diastereoselective aldol reaction, b) construction of a diazepanone with an unstable fatty‐acid side chain, and c) global deprotection with hydrogenation. This report provides a route for the synthesis of related liponucleoside antibiotics with fatty‐acid side chains.