ipomoeassin B | 850894-52-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: ipomoeassin B
• 英文别名: [(1S,3R,4S,5R,6R,8R,10S,23R,24R,25R,26R)-4,5,26-trihydroxy-6-methyl-17,20-dioxo-24-[(E)-3-phenylprop-2-enoyl]oxy-10-propyl-2,7,9,21,27-pentaoxatricyclo[21.3.1.03,8]heptacosan-25-yl] (E)-2-methylbut-2-enoate
• CAS: 850894-52-9
• 化学式: C₄₀H₅₆O₁₄
• 分子量: 760.876
• InChiKey: JMFPDJPZDSGILZ-PRDJDGSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  54
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  194
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  ipomoeassin B 、 原乙酸三乙酯 在 camphor-10-sulfonic acid 作用下， 反应 1.0h， 生成
  参考文献：
  名称：

  细胞毒性树脂糖苷伊豆素A-F及其类似物的全合成及生物学评价

  摘要：

  使用现成的化合物26作为肉桂酸的替代品的多任务C硅烷化策略代表了树脂葡糖苷皂苷的所有已知成员的全合成的关键设计要素。这种保护基团的作用是使装饰目标葡萄糖亚基的不饱和酸在合成的早期阶段附着，防止它们参与用于形成大环的钌催化的闭环复分解（RCM），并保护它们防止在威尔金森氏催化剂上氢化所得环烯烃的过程中还原。由于C-甲硅烷基可随O-一起被去除在乙腈中使用三氟甲基丙烯酸三（二甲基氨基）ulf（TASF）的TBS取代基，在最后阶段不需要单独的保护基操作，因此有助于总体上有利的“步骤经济性”。除了天然存在的叶绿素外，还通过“转移总合成”制备了一小套合成类似物。用两种不同的癌细胞系测定了这些化合物的细胞毒性。记录的数据证实了先前的发现，即这些两亲性糖缀合物的酰化和氧合模式与它们的生物活性谱高度相关。事实证明，依泊豆素F是该系列中最有前途的成员，显示出低纳摩尔范围内的IC 50值。

  DOI：

  10.1002/chem.200901449
• 作为产物：
  描述：

  2,3,4-tri-O-acetyl-D-fucopyranosyl bromide 在 4-二甲氨基吡啶 、 tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene](benzylidene)Ru(II) dichloride 、 RhCl(PPh₃)3 、 三氟化硼乙醚 、 potassium methanolate 2,6-二甲基吡啶 、 甲醇 、 三甲基氯硅烷 、 2,6-二叔丁基吡啶 、 4 A molecular sieve 、 2,4,6-三氯苯甲酰氯 、 三(二甲氨基)锍二氟三甲基硅酸 、 水 、 氢气 、 silver trifluoromethanesulfonate 、 sodium cyanoborohydride 、 对甲苯磺酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 、 甲苯 、 乙腈 、 正戊烷 为溶剂， -20.0~20.0 ℃ 、101.33 kPa 条件下， 反应 72.0h， 生成 ipomoeassin B
  参考文献：
  名称：

  Total Syntheses of Ipomoeassin B and E

  摘要：

  A concise, flexible, and efficient total synthesis of the cytotoxic resin glycosides ipomoeassin B (1) and ipomoeassin E (2) is reported which features the advantages of a novel protecting group strategy employing (Z)-3-dimethyl(phenyl)silyl-2-propenoic acid as cinnamic acid surrogate. The use of this readily available compound allowed the macrocycle of the glycolipids to be formed by ring closing olefin metathesis (RCM) with the aid of the second generation Grubbs carbene complex 12. The resulting E/Z mixture could be selectively hydrogenated using Wilkinson's catalyst [RhCl(PPh3)(3)] without affecting the unsaturated esters in the periphery of the compound, before the C-silyl group was cleaved off with TASF [tris(dimethylamino)sulfonium difluorotrimethylsilicate] under notably mild conditions to release the required cinnamate moiety. Other key steps of the synthesis route comprise the formation of the disaccharide linkage by the trichloroacetimidate method, the formation of the chiral acid segment 19 via a VO(acac)(2)-catalyzed, tert-BuOOH-induced oxidative rearrangement of the optically pure furyl alcohol (-)-15 (Achmatowicz-type reaction), and a reductive cleavage of the 4,6-O-p-methoxybenzylidene acetal in 5 with NaBH3CN and Me3SiCl (TMSCl), the regiochemical course of which was found to be opposite to that previously reported in the literature for sterically less encumbered substrates.

  DOI：

  10.1021/ja068901g

文献信息

• Morning glory-derived anticancer agents, and novel ipomoeassin compounds
  申请人：Kingston G. I. David

  公开号：US20060264383A1

  公开（公告）日：2006-11-23

  Ipomoeassin compounds derived from morning glory plant material (especially Ipomoea sp. from Suriname) are useful as anti-cancer agents. The novel compounds also are useful for treating neurodegenerative disorders (such as Alzheimer's disease) in human patients.

  从早晨荣耀植物材料（尤其是来自苏里南的早晨荣耀属植物）中提取的Ipomoeassin化合物可用作抗癌剂。这些新型化合物也可用于治疗人类患者的神经退行性疾病（如阿尔茨海默病）。
• Ipomoeassins A−E, Cytotoxic Macrocyclic Glycoresins from the Leaves of <i>Ipomoea </i><i>s</i><i>quamosa</i> from the Suriname Rainforest
  作者：Shugeng Cao、Rebecca C. Guza、Jan H. Wisse、James S. Miller、Randy Evans、David G. I. Kingston

  DOI：10.1021/np049629w

  日期：2005.4.1

  The new glycoresins, ipomoeassins A-E (1-5), have been isolated from the leaves of Ipomoea squamosa. The structures were elucidated by spectroscopic analyses and chemical transformations. The absolute configurations of C-5 (ipomoeassins 3-5) and C-11 (ipomoeassins 1 and 2) were determined by their derivatives with (R)- and (S)-MPA. All the isolates were active in the A2780 human ovarian cancer cell line assay, and 4 showed the highest activity with an IC50 value of 35 nM.
• Total Syntheses of Ipomoeassin B and E
  作者：Alois Fürstner、Takashi Nagano

  DOI：10.1021/ja068901g

  日期：2007.2.1

  A concise, flexible, and efficient total synthesis of the cytotoxic resin glycosides ipomoeassin B (1) and ipomoeassin E (2) is reported which features the advantages of a novel protecting group strategy employing (Z)-3-dimethyl(phenyl)silyl-2-propenoic acid as cinnamic acid surrogate. The use of this readily available compound allowed the macrocycle of the glycolipids to be formed by ring closing olefin metathesis (RCM) with the aid of the second generation Grubbs carbene complex 12. The resulting E/Z mixture could be selectively hydrogenated using Wilkinson's catalyst [RhCl(PPh3)(3)] without affecting the unsaturated esters in the periphery of the compound, before the C-silyl group was cleaved off with TASF [tris(dimethylamino)sulfonium difluorotrimethylsilicate] under notably mild conditions to release the required cinnamate moiety. Other key steps of the synthesis route comprise the formation of the disaccharide linkage by the trichloroacetimidate method, the formation of the chiral acid segment 19 via a VO(acac)(2)-catalyzed, tert-BuOOH-induced oxidative rearrangement of the optically pure furyl alcohol (-)-15 (Achmatowicz-type reaction), and a reductive cleavage of the 4,6-O-p-methoxybenzylidene acetal in 5 with NaBH3CN and Me3SiCl (TMSCl), the regiochemical course of which was found to be opposite to that previously reported in the literature for sterically less encumbered substrates.
• Total Synthesis and Biological Evaluation of the Cytotoxic Resin Glycosides Ipomoeassin A-F and Analogues
  作者：Takashi Nagano、Jiři Pospíšil、Guillaume Chollet、Saskia Schulthoff、Volker Hickmann、Emilie Moulin、Jennifer Herrmann、Rolf Müller、Alois Fürstner

  DOI：10.1002/chem.200901449

  日期：2009.9.28

  acid represents the key design element of a total synthesis of all known members of the ipomoeassin family of resin glyosides. This protecting group maneuver allows the unsaturated acids decorating the glucose subunit of the targets to be attached at an early phase of the synthesis, prevents their participation in the ruthenium‐catalyzed ring‐closing metathesis (RCM) used to form the macrocyclic ring,

  使用现成的化合物26作为肉桂酸的替代品的多任务C硅烷化策略代表了树脂葡糖苷皂苷的所有已知成员的全合成的关键设计要素。这种保护基团的作用是使装饰目标葡萄糖亚基的不饱和酸在合成的早期阶段附着，防止它们参与用于形成大环的钌催化的闭环复分解（RCM），并保护它们防止在威尔金森氏催化剂上氢化所得环烯烃的过程中还原。由于C-甲硅烷基可随O-一起被去除在乙腈中使用三氟甲基丙烯酸三（二甲基氨基）ulf（TASF）的TBS取代基，在最后阶段不需要单独的保护基操作，因此有助于总体上有利的“步骤经济性”。除了天然存在的叶绿素外，还通过“转移总合成”制备了一小套合成类似物。用两种不同的癌细胞系测定了这些化合物的细胞毒性。记录的数据证实了先前的发现，即这些两亲性糖缀合物的酰化和氧合模式与它们的生物活性谱高度相关。事实证明，依泊豆素F是该系列中最有前途的成员，显示出低纳摩尔范围内的IC 50值。