(Z)-3,4-bis(benzyloxy)-5-(2-(6-chloro-9H-purin-9-yl)ethylidene)furan-2(5H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (Z)-3,4-bis(benzyloxy)-5-(2-(6-chloro-9H-purin-9-yl)ethylidene)furan-2(5H)-one
• 英文别名: (5Z)-5-[2-(6-chloropurin-9-yl)ethylidene]-3,4-bis(phenylmethoxy)furan-2-one
• 化学式: C₂₅H₁₉ClN₄O₄
• 分子量: 474.903
• InChiKey: BNTDVKJVAVGLNP-ODLFYWEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  88.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-3,4-bis(benzyloxy)-5-(2-(6-chloro-9H-purin-9-yl)ethylidene)furan-2(5H)-one 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以43.3%的产率得到4-Benzyloxy-5-[2-(6-chloro-purin-9-yl)-eth-(Z)-ylidene]-3-hydroxy-5H-furan-2-one
  参考文献：
  名称：

  L-抗坏血酸的新型嘧啶和嘌呤衍生物：合成，一维和二维1H和13C NMR研究，细胞生长抑制和抗病毒评估。

  摘要：

  内酯环的C-2'（6-10）或C-2'和C-3'（11-15）位置含有游离羟基的1-抗坏血酸的新型C-5取代的嘧啶衍生物的合成被描述。2,3-O，O-二苄基-1-抗坏血酸的16-氯-和6-（N-吡咯基）嘌呤衍生物的脱苄基作用（16和17）得到了在C-2'处含有羟基的新化合物（ 18）和C-2'和C-3'（19和20）。从它们的一维和二维（1）H和（13）C NMR谱图和连接性，推导出C4'C5'双键的Z和E构型以及化合物6-9的内酯环的位置。 NOESY和HMBC光谱。在该系列所有评估的化合物中，化合物15和18表现出最佳的抑制活性。含有5-（三氟甲基）尿嘧啶的化合物15显示出对所有人类恶性细胞系（IC（50）：5.6-12.8 microM）的显着抑制活性，除了对人类T淋巴细胞。此外，该化合物还通过增加G2 / M期的细胞数量影响细胞周期，并诱导SW 620和MiaPaCa-2细胞凋亡。

  DOI：

  10.1016/j.bmc.2004.09.052
• 作为产物：
  描述：

  6-氯嘌呤 、 5-acetyl-6-bromo-2,3-dibenzyl-L-ascorbic acid 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 以61%的产率得到(Z)-3,4-bis(benzyloxy)-5-(2-(6-chloro-9H-purin-9-yl)ethylidene)furan-2(5H)-one
  参考文献：
  名称：

  Novel Pyrimidine and Purine Derivatives of l-Ascorbic Acid:  Synthesis and Biological Evaluation

  摘要：

  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.

  DOI：

  10.1021/jm991017z

文献信息

• 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.
• The novel pyrimidine and purine derivatives of l-ascorbic acid: synthesis, one- and two-dimensional 1H and 13C NMR study, cytostatic and antiviral evaluation
  作者：Tatjana Gazivoda、Miha Plevnik、Janez Plavec、Sandra Kraljević、Marijeta Kralj、Krešimir Pavelić、Jan Balzarini、Erik De Clercq、Mladen Mintas、Silvana Raić-Malić

  DOI：10.1016/j.bmc.2004.09.052

  日期：2005.1

  E-configuration of the C4'C5' double bond and position of the lactone ring of the compounds 6-9 were deduced from their one- and two-dimensional (1)H and (13)C NMR spectra and connectivities in NOESY and HMBC spectra. Compounds 15 and 18 showed the best inhibitory activities of all evaluated compounds in the series. The compound 15 containing 5-(trifluoromethyl)uracil showed marked inhibitory activity against

  内酯环的C-2'（6-10）或C-2'和C-3'（11-15）位置含有游离羟基的1-抗坏血酸的新型C-5取代的嘧啶衍生物的合成被描述。2,3-O，O-二苄基-1-抗坏血酸的16-氯-和6-（N-吡咯基）嘌呤衍生物的脱苄基作用（16和17）得到了在C-2'处含有羟基的新化合物（ 18）和C-2'和C-3'（19和20）。从它们的一维和二维（1）H和（13）C NMR谱图和连接性，推导出C4'C5'双键的Z和E构型以及化合物6-9的内酯环的位置。 NOESY和HMBC光谱。在该系列所有评估的化合物中，化合物15和18表现出最佳的抑制活性。含有5-（三氟甲基）尿嘧啶的化合物15显示出对所有人类恶性细胞系（IC（50）：5.6-12.8 microM）的显着抑制活性，除了对人类T淋巴细胞。此外，该化合物还通过增加G2 / M期的细胞数量影响细胞周期，并诱导SW 620和MiaPaCa-2细胞凋亡。