1-{5-O-(4-chlorobenzoyl)-2,3-di-O-isobutyryl-3-C-ethynyl-β-D-ribopentofuranosyl}uracil | 199787-39-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-{5-O-(4-chlorobenzoyl)-2,3-di-O-isobutyryl-3-C-ethynyl-β-D-ribopentofuranosyl}uracil
• 英文别名: 1-[5-O-(4-chlorobenzoyl)-3-C-ethynyl-2,3-di-O-isobutyryl-β-D-ribofuranosyl]uracil；[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3-ethynyl-3,4-bis(2-methylpropanoyloxy)oxolan-2-yl]methyl 4-chlorobenzoate
• CAS: 199787-39-8
• 化学式: C₂₆H₂₇ClN₂O₉
• 分子量: 546.961
• InChiKey: VPGZLHTYHFJQQZ-PJGVWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-{5-O-(4-chlorobenzoyl)-2,3-di-O-isobutyryl-3-C-ethynyl-β-D-ribopentofuranosyl}uracil 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 为溶剂， 反应 1.5h， 以92%的产率得到EUrd
  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：

  2,4-二(三甲硅氧基)嘧啶 、 5-O-(4-chlorobenzoyl)-3-C-ethynyl-1,2,3-tri-O-isobutyryl-D-ribo-pentofuranose 在 四氯化锡 作用下， 以 乙腈 为溶剂， 反应 20.0h， 以78%的产率得到1-{5-O-(4-chlorobenzoyl)-2,3-di-O-isobutyryl-3-C-ethynyl-β-D-ribopentofuranosyl}uracil
  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

文献信息

• D-PENTOFURANOSE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP0842942A1

  公开（公告）日：1998-05-20

  The present invention relates to D-pentofuranose derivatives represented by the following formulas (1) through (4): (wherein A represents a chlorobenzoyl group; R1 represents a hydrogen atom, an aliphatic lower acyl group, a substituted or unsubstituted benzoyl group; each of X and Y represents a lower alkyl group; Z represents an ethynyl group or tri-lower alkyl silylethynyl group; the sugar moiety in formula (1) represents xylose; and the sugar moiety of each of formulas (3) and (4) represents ribose). The present invention also relates to a process for preparing the compound (2) characterized by oxidizing the compound of formula (1) with a hypochlorite in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidinoxy compound. These compounds are useful as intermediates in the synthesis of 3'-C-substituted ribonucleoside derivatives having excellent antitumor activities.

  本发明涉及由下式(1)至(4)代表的D-戊呋喃糖衍生物： (其中A代表氯代苯甲酰基；R1代表氢原子、脂肪族低级酰基、取代或未取代的苯甲酰基；X和Y各自代表低级烷基；Z代表乙炔基或三低级烷基硅烷基乙炔基；式(1)中的糖基代表木糖；式(3)和(4)各自的糖基代表核糖)。本发明还涉及一种制备化合物（2）的工艺，其特征是在催化量的 2，2，6，6-四甲基哌啶氧基化合物存在下，用次氯酸盐氧化式（1）化合物。 这些化合物可作为合成 3'-C 取代的核糖核苷衍生物的中间体，具有优异的抗肿瘤活性。
• US5880294A
  申请人：——

  公开号：US5880294A

  公开（公告）日：1999-03-09