(3R,4S)-1-(tert-butoxycarbonyl)-3-triisopropylsiloxy-4-[(S)-2,2-dimethylcyclopropyl]azetidin-2-one | 201044-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3R,4S)-1-(tert-butoxycarbonyl)-3-triisopropylsiloxy-4-[(S)-2,2-dimethylcyclopropyl]azetidin-2-one
• 英文别名: tert-butyl (2S,3R)-2-[(1S)-2,2-dimethylcyclopropyl]-4-oxo-3-tri(propan-2-yl)silyloxyazetidine-1-carboxylate
• CAS: 201044-90-8
• 化学式: C₂₂H₄₁NO₄Si
• 分子量: 411.657
• InChiKey: XBYZGKKQUDEEJG-FGTMMUONSA-N

物化性质

• 沸点：
  453.632±38.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.017±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,4S)-1-(tert-butoxycarbonyl)-3-triisopropylsiloxy-4-[(S)-2,2-dimethylcyclopropyl]azetidin-2-one 在 4-二甲氨基吡啶 、 氢氟酸 、 三乙胺 作用下， 以 吡啶 为溶剂， 生成 methyl (2R,3S)-3-[(1S)-2,2-dimethylcyclopropyl]-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
  参考文献：
  名称：

  Efficient Asymmetric Syntheses of β-Lactams Bearing a Cyclopropane or an Epoxide Moiety and Their Application to the Syntheses of Novel Isoserines and Taxoids

  摘要：

  DOI：

  10.1021/jo971908j
• 作为产物：
  描述：

  (3R,4S)-4-[(1S)-2,2-dimethylcyclopropyl]-3-hydroxy-1-(4-methoxyphenyl)azetidin-2-one 在 4-二甲氨基吡啶 、 ammonium cerium(IV) nitrate 、 三乙胺 作用下， 生成 (3R,4S)-1-(tert-butoxycarbonyl)-3-triisopropylsiloxy-4-[(S)-2,2-dimethylcyclopropyl]azetidin-2-one
  参考文献：
  名称：

  Efficient Asymmetric Syntheses of β-Lactams Bearing a Cyclopropane or an Epoxide Moiety and Their Application to the Syntheses of Novel Isoserines and Taxoids

  摘要：

  DOI：

  10.1021/jo971908j

文献信息

• Synthesis and structure-activity relationships of new second-generation taxoids
  作者：Iwao Ojima、Tao Wang、Michael L. Miller、Songnian Lin、Christopher P. Borella、Xudong Geng、Paula Pera、Rapph J. Bernacki

  DOI：10.1016/s0960-894x(99)00629-0

  日期：1999.12

  A series of second-generation taxoids bearing a substituent on the C-2-benzoyl group and modifications at C-3'/C-10 positions was synthesized. These taxoids exhibited 2-3 orders of magnitude higher potency than that of paclitaxel against drug-resistant human breast cancer cell lines. It is also noteworthy that three taxoids showed almost no difference in activity against drug-resistant and drug-sensitive

  合成了一系列在C-2-苯甲酰基上带有取代基并在C-3'/ C-10位置进行修饰的第二代紫杉醇。这些紫杉醇对紫杉醇抗药性的人乳腺癌细胞系的效能比紫杉醇高2-3个数量级。还值得注意的是，三种类生物碱对抗药性和药物敏感性细胞系的活性几乎没有差异，它们被归类为“高级第二代类生物碱”。
• Design, Synthesis, and Biological Evaluation of New-Generation Taxoids
  作者：Iwao Ojima、Jin Chen、Liang Sun、Christopher P. Borella、Tao Wang、Michael L. Miller、Songnian Lin、Xudong Geng、Larisa Kuznetsova、Chuanxing Qu、David Gallager、Xianrui Zhao、Ilaria Zanardi、Shujun Xia、Susan B. Horwitz、Jon Mallen-St. Clair、Jennifer L. Guerriero、Dafna Bar-Sagi、Jean M. Veith、Paula Pera、Ralph J. Bernacki

  DOI：10.1021/jm800086e

  日期：2008.6.1

  Novel second-generation taxoids with systematic modifications at the C2, C10, and C3'N positions were synthesized and their structure-activity relationships studied. A number of these taxoids exhibited exceptionally high potency against multidrug-resistant cell lines, and several taxoids exhibited virtually no difference in potency against the drug-sensitive and drug-resistant cell lines. These exceptionally potent taxoids were termed "third-generation taxoids". 19 (SB-T-1214), 14g(SB-T-121303), and 14i (SB-T-1213031) exhibited excellent activity against paclitaxel-resistant ovarian cancer cell lines with mutations in beta-tubulin as well, wherein the drug resistance is mediated by the beta-tubulin mutation. These taxoids were found to possess exceptional activity in promoting tubulin assembly, forming numerous very short microtubules similar to those formed by discodermolide. Taxoids 19 and 14g also showed excellent cytotoxicity against four pancreatic cancer cell lines, expressing three to four multidrug-resistant genes. Moreover, taxoid 19 exhibited excellent in vivo efficacy against highly drug-resistant CFPAC-1 pancreatic as well as DLD-1 human colon tumor xenografts in mice.
• Efficient Asymmetric Syntheses of β-Lactams Bearing a Cyclopropane or an Epoxide Moiety and Their Application to the Syntheses of Novel Isoserines and Taxoids
  作者：Iwao Ojima、Songnian Lin

  DOI：10.1021/jo971908j

  日期：1998.1.1