2,3-di-O-benzyl-4-(5,6)-epoxy-L-ascorbic acid | 318239-79-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: 2,3-di-O-benzyl-4-(5,6)-epoxy-L-ascorbic acid
• 英文别名: 2,3-O,O-dibenzyl-4-(5,6-epoxy)-L-ascorbic acid；4-(5,6-epoxy)-2,3-O,O-dibenzyl-L-ascorbic acid；5,6-anhydro-2,3-di-O-benzyl-L-ascorbic acid；4-(5,6-epoxy)-2,3-di-O-benzyl-L-ascorbic acid；(2R)-2-[(2S)-oxiran-2-yl]-3,4-bis(phenylmethoxy)-2H-furan-5-one
• CAS: 318239-79-1
• 化学式: C₂₀H₁₈O₅
• 分子量: 338.36
• InChiKey: GWEOAIVNJJEWCX-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-di-O-benzyl-4-(5,6)-epoxy-L-ascorbic acid 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 水 、 乙腈 为溶剂， 70.0 ℃ 、482.64 kPa 条件下， 反应 96.0h， 生成
  参考文献：
  名称：

  一类不寻常氨基酸的合成，酶活性和X射线晶体学。

  摘要：

  描述了两种新氨基酸，天然糖苷酶抑制剂的氮类似物salacinol的合成，其中含有羧酸盐内盐，以及果蝇果蝇高尔基甘露糖苷酶II（dGMII）活性位点中这些类似物之一的晶体结构。 。Salacinol是天然存在的sulf离子，是Salacia reticulata水提取物中的活性成分之一，传统上在斯里兰卡和印度用于治疗糖尿病。合成策略依赖于2,5,5-脱水- 2,3-二-O-苄基-1-抗坏血酸产生偶联的加合物。脱保护，立体选择性催化还原和偶联产物的水解得到目标化合物。衍生自d-阿拉伯糖醇的化合物抑制dGMII（糖蛋白加工途径中的关键酶之一），IC（50）为0.3mM。抑制GMII已被确定为控制转移性癌症的靶标。该化合物与dGMII的复合物的X射线晶体结构提供了对有效抑制剂的需求的见解。相同的化合物抑制重组人麦芽糖酶葡糖淀粉酶，后者是参与小肠中葡萄糖寡糖分解的关键肠酶之一，K（i）值为21mic

  DOI：

  10.1016/j.bmc.2006.09.004
• 作为产物：
  描述：

  维生素 C 在 氢溴酸 、 sodium carbonate 、 potassium carbonate 作用下， 以 溶剂黄146 为溶剂， 生成 2,3-di-O-benzyl-4-(5,6)-epoxy-L-ascorbic acid
  参考文献：
  名称：

  一些l-抗坏血酸衍生物的晶体结构、圆二色光谱和绝对构型

  摘要：

  摘要 通过 X 射线晶体学研究了具有 4-(5,6-环氧)- (4) 和 6-O-甲苯磺酰基- (8) 官能团的 l-抗坏血酸的手性 2,3-O,O-二苄基醚和圆二色性 (CD) 光谱。2,3-O,O-二苄基-5,6-异亚丙基-1-抗坏血酸(6) 和8 的立体结构通过X 射线晶体结构分析确定。4 和 8 的 CD 光谱与其合成前体 (2-3、5-7) 和 l-抗坏血酸 (1) 本身的 CD 光谱的比较，以及 6 和 8 的晶体结构允许推断4的绝对构型。因此，4中的手性原子C-4和C-5具有R和S构型，这与1的构型一致。

  DOI：

  10.1016/j.molstruc.2003.09.019

文献信息

• GLYCOSIDASE INHIBITORS AND METHODS OF SYNTHESIZING SAME
  申请人：Pinto M. Brian

  公开号：US20070244184A1

  公开（公告）日：2007-10-18

  The compounds of the present invention relate to chain-extended and chain-modified analogues of salacinol, including embodiments where the sulfate moiety has been substituted with a carboxylate or phosphate moiety. In other embodiments the sulfate moiety has been shifted by one carbon atom in the zwitterionic structure. In another embodiment the polyhydroxylated side chain may be replaced with a lipophilic alkyl chain and a suitable counterion. The invention also encompasses methods for synthesizing the salacinol analogues and using the analogues for enzyme inhibition applications.

  本发明的化合物涉及与salacinol的链延伸和链修饰类似物，包括其中硫酸酯基团已被羧酸酯基团或磷酸酯基团取代的实施例。在其他实施例中，硫酸酯基团在带电离结构中已被向一碳原子移位。在另一实施例中，多羟基侧链可以被脂溶性烷基链和适当的对离子取代。本发明还涵盖了合成salacinol类似物的方法以及将这些类似物用于酶抑制应用的方法。
• The new 5- or 6-azapyrimidine and cyanuric acid derivatives of l-ascorbic acid bearing the free C-5 hydroxy or C-4 amino group at the ethylenic spacer: CD-spectral absolute configuration determination and biological activity evaluations
  作者：K. Wittine、M. Stipković Babić、M. Košutić、M. Cetina、K. Rissanen、S. Kraljević Pavelić、A. Tomljenović Paravić、M. Sedić、K. Pavelić、M. Mintas

  DOI：10.1016/j.ejmech.2011.03.066

  日期：2011.7

  6-azauracil (17) and cyanuric acid (21) derivatives of l-ascorbic acid bearing free amino group at ethylenic spacer existed as a racemic mixture of enantiomers, whereas L-ascorbic derivatives containing the C-5 substituted hydroxy group at the ethylenic spacer were obtained in (4R, 5S) enantiomeric form. The stereochemistry of 6-azauracil derivative of l-ascorbic acid (13) was confirmed by X-ray crystal structure

  我们对新颖类型胞嘧啶和5-氮杂胞嘧啶（的合成报告19），尿嘧啶和6-氮尿嘧啶（13 - 18和氰尿酸（）19 - 22）的衍生物升抗坏血酸，以及它们的抑制细胞生长的人体恶性肿瘤细胞系与肝癌细胞活性的评价。它们对人正常成纤维细胞（WI38）的细胞毒性作用。CD谱分析表明，胞嘧啶（5和6），尿嘧啶（14 - 16），6-氮尿嘧啶（17），氰尿酸（21）的衍生物升-在烯键间隔基上带有游离氨基的抗坏血酸以对映异构体的外消旋混合物的形式存在，而在烯键间隔基上含有C -5取代羟基的L-抗坏血酸衍生物以（4 R， 5 S）对映体形式获得。通过X射线晶体结构分析证实了1-抗坏血酸（13）的6-氮杂尿嘧啶衍生物的立体化学。这些分子通过一个N–H⋯O氢键，两个C–H⋯O氢键和两个C–H⋯π相互作用自组装成三维框架。细胞抑制活性评估表明化合物对测试的细胞系没有显示出明显的抗增殖作用。但是，l的胞嘧啶衍生物-含有C
• Novel 1,2,4-triazole and imidazole derivatives of l-ascorbic and imino-ascorbic acid: Synthesis, anti-HCV and antitumor activity evaluations
  作者：Karlo Wittine、Maja Stipković Babić、Damjan Makuc、Janez Plavec、Sandra Kraljević Pavelić、Mirela Sedić、Krešimir Pavelić、Pieter Leyssen、Johan Neyts、Jan Balzarini、Mladen Mintas

  DOI：10.1016/j.bmc.2012.01.054

  日期：2012.6

  Several novel 1,2,4-triazole and imidazole L-ascorbic acid (1, 2, 3, 5, 6 and 9) and imino-ascorbic acid (4, 7 and 8) derivatives were prepared and evaluated for their inhibitory activity against hepatitis C virus (HCV) replication and human tumour cell proliferation. Compounds 6 and 9 exerted the most pronounced cytostatic effects in all tumour cell lines tested, and were highly selective for human T-cell acute lymphoblastic leukaemia cells (CEM/0) with IC(50)s of 10 +/- 4 and 7.3 +/- 0.1 mu M, respectively. Unlike compound 9, compound 6 showed no toxicity in human diploid fibroblasts. One of the possible mechanisms of action of compound 6 accounting for observed cytostatic activity towards haematological malignancies might be inhibition of inosine monophosphate dehydrogenase (IMPDH) activity, a key enzyme of de novo purine nucleotide biosynthesis providing the cells with precursors for DNA and RNA synthesis indispensable for cell growth and division, which has emerged as an important target for antileukemic therapy. In addition, this compound proved to be the most potent inhibitor of the hepatitis C virus replication as well. However, observed antiviral effect was most likely associated with the effect that the compound exerted on the host cell rather than with selective effect on the replication of the virus itself. In conclusion, results of this study put forward compound 6 as a potential novel antitumor agent (IMPDH inhibitor) for treating leukaemia. Its significant biological activity and low toxicity in human diploid fibroblasts encourage further development of this compound as a lead. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives of 2,3-<i>O</i>,<i>O</i>-Dibenzyl-6-deoxy-<scp>l</scp>-ascorbic Acid and 4,5-Didehydro-5,6- dideoxy-<scp>l</scp>-ascorbic Acid
  作者：Silvana Raić-Malić、Draženka Svedružić、Tatjana Gazivoda、Andreja Marunović、Antonija Hergold-Brundić、Ante Nagl、Jan Balzarini、Erik De Clercq、Mladen Mintas

  DOI：10.1021/jm0009540

  日期：2000.12.1

  The new pyrimidine derivatives of 2,3-O,O-dibenzyl-6-deoxy-L-ascorbic acid (8-10) were synthesized by condensation of uracil and its 5-fluoro- and 5-trifluoromethyl-substituted derivatives with 4-(5,6-epoxypropyl)-2,3-O,O-dibenzyl-L-ascorbic acid (7), while pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-L-ascorbic acid (14-17) with free C-2' and C-3' hydroxy groups in the lactone ring were obtained by debenzylation of 11-13 with boron trichloride. Z-Configuration of the C4'=C5' double bond and position of the benzyl group in the lactone ring of 14 were deduced from their H-1 and C-13 NMR spectra and connectivities in COSY, ROESY, and HMBC spectra. The exact stereostructure of 13 was confirmed by its X-ray crystal structure analysis. Of all the compounds in the series, compound 16 containing a 5-fluoro-substituted uracil ring showed the most significant antitumor activities against murine leukemia L1210/0 (IC50 = 1.4 mug/mL), murine mammary carcinoma FM3A/0 (IC50 = 0.78 mug/mL), and, to a lesser extent, human T-lymphocyte cells Molt4/C8 (IC50 = 31.8 mug/mL) and CEM/0 cell lines (IC50 = 20.9 mug/mL).
• Crystal structures, circular dichroism spectra and absolute configurations of some l-ascorbic acid derivatives
  作者：Karlo Wittine、Tatjana Gazivoda、Marko Markuš、Draginja Mrvoš-Sermek、Antonija Hergold-Brundić、Mario Cetina、Dinko Žiher、Vesna Gabelica、Mladen Mintas、Silvana Raić-Malić

  DOI：10.1016/j.molstruc.2003.09.019

  日期：2004.1

  synthetic precursors (2–3, 5–7) and l -ascorbic acid (1) itself, as well as crystal structures of 6 and 8 permitted to deduce the absolute configuration of 4. Thus, the chiral atoms C-4 and C-5 in 4 have R and S configurations, which is consistent with the configuration of 1.

  摘要 通过 X 射线晶体学研究了具有 4-(5,6-环氧)- (4) 和 6-O-甲苯磺酰基- (8) 官能团的 l-抗坏血酸的手性 2,3-O,O-二苄基醚和圆二色性 (CD) 光谱。2,3-O,O-二苄基-5,6-异亚丙基-1-抗坏血酸(6) 和8 的立体结构通过X 射线晶体结构分析确定。4 和 8 的 CD 光谱与其合成前体 (2-3、5-7) 和 l-抗坏血酸 (1) 本身的 CD 光谱的比较，以及 6 和 8 的晶体结构允许推断4的绝对构型。因此，4中的手性原子C-4和C-5具有R和S构型，这与1的构型一致。