methyl 2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribofuranose | 182825-16-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribofuranose
• 英文别名: methyl 2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribo-pentofuranoside；[(2R,3R,4R)-3,4-dibenzoyloxy-3-ethynyl-5-methoxyoxolan-2-yl]methyl benzoate
• CAS: 182825-16-7
• 化学式: C₂₉H₂₄O₈
• 分子量: 500.505
• InChiKey: ZNBXPAHNTVTRHZ-LADWPMNLSA-N

物化性质

• 沸点：
  608.2±55.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 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：

  methyl 2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribofuranose 在 硫酸 、 氨 、 四氯化锡 作用下， 以 甲醇 、 溶剂黄146 、 乙腈 为溶剂， 生成 乙炔基胞苷
  参考文献：
  名称：

  Nucleosides and nucleotides. Part 212: Practical large-scale synthesis of 1-(3-C-ethynyl-β-d-ribo-pentofuranosyl)cytosine (ECyd), a potent antitumor nucleoside. Isobutyryloxy group as an efficient anomeric leaving group in the Vorbrüggen glycosylation reaction

  摘要：

  A practical synthetic route to the antitumor nucleoside, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, 1) from 1,2-O-isopropylidene-D-xylofuranose (3) has been developed. Since most of the compounds were obtained as crystals, the target ECyd was prepared without any chromatographic purification in 31% overall yield from compound 3. The isobutyryloxy group was found to be an effective leaving group at the anomeric position of the 3-beta-C-ethynyl glycosyl donors in the key Vorbruggen glycosylation reaction. Using a similar procedure without chromatographic purification, the uracil congener EUrd [1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (2), which also has a potent antitumor effect, was synthesized from 3 in 39% overall yield. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(01)01249-2
• 作为产物：
  描述：

  5-O-(tert-butyldimethylsilyl)-1,2-O-isopropylidene-α-D-erythro-pentofuranos-3-ulose 在 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 正丁基锂 、 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 methyl 2,3,5-tri-O-benzoyl-3-C-ethynyl-α,β-D-ribofuranose
  参考文献：
  名称：

  Nucleosides and nucleotides. 152. 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside

  摘要：

  1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) has been designed as a potential multifunctional antitumor nucleoside antimetabolite. EUrd was synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-alpha,beta-D-ribo-pentofuranose (6) and bis(trimethylsilyl)uracil in the presence of trimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH3/MeOH. In vitro tumor cell growth inhibitory activity of EUrd against 14 human solid tumor cell lines was compared with 5-fluorouridine (FUrd), 2'-deoxy-5-fluorouridine (FdUrd), and 5-fluorouracil (5-FU) as positive controls. EUrd was a quite potent tumor cell growth inhibitor against almost ail the tumor cell lines examined in this study except for human pancreas PANC-1 cells, and the potency of EUrd is about 6 to 650 times stronger than that of 5-FU and comparable to that of FUrd and FdUrd. EUrd showed also potent antitumor activity against human tumors as xenografts in nude mice when given in a daily intravenous dose of 2 mg/kg on consecutive days. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00339-3

文献信息

• 3'-SUBSTITUTED NUCLEOSIDE DERIVATIVES
  申请人：TAIHO PHARMACEUTICAL CO., LTD.

  公开号：EP0747389A1

  公开（公告）日：1996-12-11

  The invention relates to a 3'-substituted nucleoside derivative represented by the following general formula (1): wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: in which Ra, Rb and Rc are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R1 and R2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3'-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.

  本发明涉及由以下通式（1）代表的 3'-取代的核苷衍生物： 其中 B 表示可具有取代基的核酸碱基，Z 表示可被式中代表的基团取代的低级炔基或低级烯基： 其中，Ra、Rb 和 Rc 分别为低级烷基或苯基，或可具有至少一个低级烷基的环氧乙烷基，R1 和 R2 分别代表 H 或可容易地留在生物体内的酯形成残基，R3 为 H、单磷酸或多磷酸残基或可容易地留在生物体内的酯形成残基，但糖基为核糖或其药学上可接受的盐。根据本发明，3'-取代的核苷衍生物具有优异的抗肿瘤活性，因此可用于治疗和预防癌症。
• Nucleosides and Nucleotides. 158. 1-(3-<i>C</i>-Ethynyl<b>-</b>β-<scp>d</scp>-<i>ribo</i>-pentofuranosyl)- cytosine, 1-(3-<i>C</i>-Ethynyl-β-<scp>d</scp>-<i>ribo</i>-pentofuranosyl)uracil, and Their Nucleobase Analogues as New Potential Multifunctional Antitumor Nucleosides with a Broad Spectrum of Activity
  作者：Hideshi Hattori、Motohiro Tanaka、Masakazu Fukushima、Takuma Sasaki、Akira Matsuda

  DOI：10.1021/jm960537g

  日期：1996.1.1

  We previously designed 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) as a potential multifunctional antitumor nucleoside antimetabolite. It showed a potent and broad spectrum of antitumor activity against various human tumor cells in vitro and in vivo. To determine the structure-activity relationship, various nucleobase analogues of EUrd, such as 5-fluorouracil, thymine, cytosine, 5-fluorocytosine, adenine, and guanine derivatives, were synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-alpha,beta-D-ribo-pentofuranose (6) and the corresponding pertrimethylsilylated nucleobases in the presence of SnCl4 or TIMSOTf as a Lewis acid in CH3CN followed by debenzoylation. The in vitro tumor cell growth inhibitory activity of these 3'-C-ethynyl nucleosides against mouse leukemia L1210 and human nasopharyngeal KB cells showed that 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and EUrd were the most potent inhibitors in the series, with IC50 values for L1210 cells of 0.016 and 0.13 mu M and for KB cells of 0.028 and 0.029 mu M, respectively. 5-Fluorocytosine, 5-fluorouracil, and adenine nucleosides showed much lower activity, with IC50 values of 0.4-2.5 mu M, while thymine and guanine nucleosides did not exhibit any activity up to 300 mu M. We next evaluated the tumor cell growth inhibitory activity of ECyd and EUrd against 36 human tumor cell lines in vitro and found that they were highly effective against these cell lines with IC50 values in the nanomolar to micromolar range. These nucleosides have a similar inhibitory spectrum. The in vivo antitumor activities of ECyd and EUrd were compared to that of 5-fluorouracil against 11 human tumor xenografts including three stomach, three colon, two pancreas, one renal, one breast, and one bile duct cancers. ECyd and EUrd showed a potent tumor inhibition ratio (73-92% inhibition relative to the control) in 9 of 11 and 8 of 11 human tumors, respectively, when administered intravenously for 10 consecutive days at doses of 0.25 and 2.0 mg/kg, respectively, while 5-fluorouracil showed potent inhibitory activity against only one tumor. Such excellent antitumor activity suggests that ECyd and EUrd are worth evaluating further for use in the treatment of human cancers.
• US5763418A
  申请人：——

  公开号：US5763418A

  公开（公告）日：1998-06-09
• USRE38090E1
  申请人：——

  公开号：USRE38090E1

  公开（公告）日：2003-04-22
• Nucleosides and nucleotides. Part 212: Practical large-scale synthesis of 1-(3-C-ethynyl-β-d-ribo-pentofuranosyl)cytosine (ECyd), a potent antitumor nucleoside. Isobutyryloxy group as an efficient anomeric leaving group in the Vorbrüggen glycosylation reaction
  作者：Makoto Nomura、Tsutomu Sato、Masato Washinosu、Motoaki Tanaka、Tetsuji Asao、Satoshi Shuto、Akira Matsuda

  DOI：10.1016/s0040-4020(01)01249-2

  日期：2002.2

  A practical synthetic route to the antitumor nucleoside, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, 1) from 1,2-O-isopropylidene-D-xylofuranose (3) has been developed. Since most of the compounds were obtained as crystals, the target ECyd was prepared without any chromatographic purification in 31% overall yield from compound 3. The isobutyryloxy group was found to be an effective leaving group at the anomeric position of the 3-beta-C-ethynyl glycosyl donors in the key Vorbruggen glycosylation reaction. Using a similar procedure without chromatographic purification, the uracil congener EUrd [1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (2), which also has a potent antitumor effect, was synthesized from 3 in 39% overall yield. (C) 2002 Elsevier Science Ltd. All rights reserved.