5,6-di-O-acetyl-2,3-di-O-benzyl-L-ascorbic acid | 231619-90-2

• 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: 5,6-di-O-acetyl-2,3-di-O-benzyl-L-ascorbic acid
• 英文别名: [(2S)-2-acetyloxy-2-[(2R)-5-oxo-3,4-bis(phenylmethoxy)-2H-furan-2-yl]ethyl] acetate
• CAS: 231619-90-2
• 化学式: C₂₄H₂₄O₈
• 分子量: 440.45
• InChiKey: VTVKICGMVADLTO-LEWJYISDSA-N

物化性质

• 熔点：
  83-86 °C
• 沸点：
  566.5±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  97.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5,6-di-O-acetyl-2,3-di-O-benzyl-L-ascorbic acid 在 硫酸氢铵 、 氨 、 六甲基二硅氮烷 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 40.0h， 生成 1-[2-(2-amino-3,4-bis-benzyloxy-5-oxo-2,5-dihydro-furan-2-yl)-ethyl]-[1,3,5]triazinane-2,4,6-trione
  参考文献：
  名称：

  l-抗坏血酸的新的5或6-氮杂嘧啶和氰尿酸衍生物，在烯键间隔基上带有游离C -5羟基或C -4氨基：CD光谱绝对构型测定和生物活性评估

  摘要：

  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

  DOI：

  10.1016/j.ejmech.2011.03.066
• 作为产物：
  描述：

  乙酸酐 、 (2R)-3,4-dibenzyloxy-2-[(1S)-1,2-dihydroxyethyl]-2H-furan-5-one 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以67%的产率得到5,6-di-O-acetyl-2,3-di-O-benzyl-L-ascorbic acid
  参考文献：
  名称：

  Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives of 2,3-O,O-Dibenzyl-6-deoxy-l-ascorbic Acid and 4,5-Didehydro-5,6- dideoxy-l-ascorbic Acid

  摘要：

  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).

  DOI：

  10.1021/jm0009540

文献信息

• Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2,3-<i>d</i>]pyrimidine 4‘,5‘-Didehydro-<scp>l</scp>-ascorbic Acid Derivatives
  作者：Tatjana Gazivoda、Mario Šokčević、Marijeta Kralj、Lidija Šuman、Krešimir Pavelić、Erik De Clercq、Graciela Andrei、Robert Snoeck、Jan Balzarini、Mladen Mintas、Silvana Raić-Malić

  DOI：10.1021/jm070324z

  日期：2007.8.1

  The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d] pyrimidine derivatives (12-22) of L-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'- didehydro-5',6'-dideoxy-L-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of L-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 mu M). Pyrimidine derivatives of L-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3- 37 mu M) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[ 2,3-d] pyrimidine derivative (12) and 6-p-bromophenylfuro[2,3-d] pyrimidine derivative (19) showed the highest cytostatic activity (IC50) 4.5- 20 mu M), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 AM, respectively, for compounds 3 and 9) at a similar to 5-fold lower concentration than that required to show cytotoxicity.
• Novel halogenated 3-deazapurine, 7-deazapurine and alkylated 9-deazapurine derivatives of l-ascorbic or imino-l-ascorbic acid: Synthesis, antitumour and antiviral activity evaluations
  作者：Maja Stipković Babić、Damjan Makuc、Janez Plavec、Tamara Martinović、Sandra Kraljević Pavelić、Krešimir Pavelić、Robert Snoeck、Graciela Andrei、Dominique Schols、Karlo Wittine、Mladen Mintas

  DOI：10.1016/j.ejmech.2015.08.008

  日期：2015.9

  Keeping the potential synergy of biological activity of synthetic anomalous derivatives of deazapurines and L-ascorbic acid (L-AA) in mind, we have synthesized new 3-, 7- and 9-deazapurine derivatives of L-ascorbic (1-4, 8-10, 13-15) and imino-L-ascorbic acid (5-7, 11, 12, 16-19). These novel compounds were evaluated for their cytostatic and antiviral activity in vitro against a panel of human malignant tumour cell lines and normal murine fibroblasts (3T3). Among all evaluated compounds, the 9-deazapurine derivative of L-AA (13) exerted the most potent inhibitory activity on the growth of CEM/0 cells (IC50 = 4.1 +/- 1.8 mu M) and strong antiproliferative effect against L1210/0 (IC50 = 4.7 +/- 0.1 mu M) while the 9-deazahypoxanthine derivative of L-AA (15) showed the best effect against HeLa cells (IC50 = 5.6 +/- 1.3 mu M) and prominent effect on L1210/0 (IC50 = 4.5 +/- 0.5 mu M). Furthermore, the 9-deazapurine derivative disubstituted with two imino-L-AA moieties (18) showed the best activity against L1210/0 tumour cells (IC50 = 4.4 +/- 0.3 mu M) and the most pronounced antiproliferative effects against MiaPaCa-2 cells (IC50 = 5.7 +/- 0.2 mu M). All these compounds showed selective cytostatic effect on tumour cell lines in comparison with embryonal murine fibroblasts (3T3). When evaluating their antiviral activity, the 3-deazapurine derivative of L-AA (3) exhibited the highest activity against both laboratory-adapted strains of human cytomegalovirus (HCMV) (AD-169 and Davis) with EC50 values comparable to those of the well-known anti-HCMV drug ganciclovir and without cytotoxic effects on normal human embryonal lung (HEL) cells. (C) 2015 Elsevier Masson SAS. All rights reserved.
• The novel C-5 aryl, alkenyl, and alkynyl substituted uracil derivatives of l-ascorbic acid: Synthesis, cytostatic, and antiviral activity evaluations
  作者：Tatjana Gazivoda、Silvana Raić-Malić、Marko Marjanović、Marijeta Kralj、Krešimir Pavelić、Jan Balzarini、Erik De Clercq、Mladen Mintas

  DOI：10.1016/j.bmc.2006.10.046

  日期：2007.1

  The novel C-5 substituted uracil derivatives Of L-ascorbic acid were synthesized by coupling of 5-iodouracil-4,5-didehydro-5,6-dideoxy-L-ascorbic acid with unsaturated stannanes under Stille reaction conditions. The new compounds were evaluated for their antitumoral and antiviral activities. Among all compounds evaluated the 5-propynyl substituted uracil derivative of L-ascorbic acid (7) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50: 0.2-0.78 PM). However, this compound was also cytotoxic to human normal fibroblasts WI 38. The 5-(phenylethynyl)uracil-2,3-di-O-benzylated L-ascorbic acid derivative (4) exhibited an albeit slight (IC50: 55-108 mu M), but selective inhibitory effect toward all tumor cell lines except for cervical carcinoma (HeLa), pancreatic carcinoma (MiaPaCa-2), laryngeal carcinoma (Hep-2), and colon carcinoma (SW 620), and no cytotoxicity to normal human fibroblast (WI 38). Compound 7 showed some, not highly specific, inhibitory potential against vesicular stomatitis virus, Coxsackie 134 virus, and Sindbis viruses (EC50: 1.6 mu M). (c) 2006 Elsevier Ltd. All rights reserved.
• 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.
• Novel Pyrimidine and Purine Derivatives of <scp>l</scp>-Ascorbic Acid:  Synthesis and Biological Evaluation
  作者：Silvana Raić-Malić、Antonija Hergold-Brundić、Ante Nagl、Mira Grdiša、Krešimir Pavelić、Erik De Clercq、Mladen Mintas

  DOI：10.1021/jm991017z

  日期：1999.7.1

  The novel pyrimidine derivatives 1-6 of 2,3-dibenzyl-4,5-didehydro-5,6-dideoxy-L-ascorbic acid were synthesized by the condensation of pyrimidine bases with 5,6-diacetyl-2,3-dibenzyl-L-ascorbic acid (DDA). Both N-9 (7) and N-7 (8) regioisomers were obtained in the reaction of 6-chloropurine with 5-acetyl-6-bromo-2,3-dibenzyl-L-ascorbic acid (ABDA), while the reaction of 6-(N-pyrrolyl)purine with ABDA afforded exclusively the N-9 isomer 9. Structures of all newly prepared compounds were deduced from the chemical shifts in H-1 and C-13 NMR spectra, as well as connectivities in 2D homo- and heteronuclear correlation spectra. An unambiguous proof of the structure and conformation of 7 was obtained by X-ray crystallographic analysis. Compounds 1-9 were found to exert cytostatic activities against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), murine leukemia (L1210/0), murine mammary carcinoma (FM3A), and human T-lymphocytes (Molt4/C8 and CEM/0), as well as antiviral activities against varicella-zoster virus (TK(+)VZV and TK(-)VZV) and cytomegalovirus (CMV). The compound 6 containing a trifluoromethyl-substituted uracil ring exhibited marked antitumor activity. The N-7-substituted purine regioisomer 8 had greater inhibitory effects on the murine L1210/0 and human CEM/0 cell lines than the N-9 isomer 7. Compound 9 with the B-purine-substituted pyrrolo moiety had a more pronounced selective cytostatic activity against human (Molt4/C8 and CEM-0) cell lines than murine (L1210/0 and FM3A/O) and human (MiaPaCa2, MCF7, HeLa, and Hep2) tumor cell lines and normal fibroblasts (Hef522). The compound 6 exhibited the most potent antiviral activities against TK(+)VZV, TK(-)VZV, and CMV, albeit at concentrations that were only slightly lower than the cytotoxic concentrations.