(3R,4S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-oxo-4-phenyl-azetidine-1-carboxylic acid tert-butyl ester | 152089-13-9

• 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)-3-(tert-Butyl-dimethyl-silanyloxy)-2-oxo-4-phenyl-azetidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3R,4S)-3-[tert-butyl(dimethyl)silyl]oxy-2-oxo-4-phenylazetidine-1-carboxylate
• CAS: 152089-13-9
• 化学式: C₂₀H₃₁NO₄Si
• 分子量: 377.556
• InChiKey: LMIWBLPJPQVTDX-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 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)-3-(tert-Butyl-dimethyl-silanyloxy)-2-oxo-4-phenyl-azetidine-1-carboxylic acid tert-butyl ester 在 sodium periodate 、 四氧化锇 、 N-甲基吗啉氧化物 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Orally active docetaxel analogue

  摘要：

  To improve cytotoxicity of 10-deoxy-10-C-morpholinoethyl docetaxel analogues against various turner cell lines including resistant cells expressing P-glycoprotein (P-gp), we modified the 7-hydroxyl group to hydrophobic groups (methoxy, deoxy, 6,7-olefin, alpha -F, 7-beta -8-beta -methano, fluoromethoxy). Among these analogues. the 7-methoxy analogue showed the strongest cytotoxicity. This analogue showed potent activity against B16 melanoma BL6 in a vivo by oral administration. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00682-x
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (3R,4S)-3-TBDMS-O-4-phenyl-2-azetidinone 生成 (3R,4S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-oxo-4-phenyl-azetidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  A highly efficient route to taxotere by the β-Lactam Synthon Method

  摘要：

  Taxotere, a highly promising anticancer drug, is synthesized through an efficient coupling of 7,10-diTroc-10-deacetylbaccatin III with enantiomerically pure (3R,4S)-1-(t)BOC-3-EEO-4-phenylazetidin-2-one which is obtained via chiral ester enolate - imine cyclocondensation.

  DOI：

  10.1016/s0040-4039(00)60514-2

文献信息

• 一种半合成紫杉烷衍生物及其制备方法和应 用
  申请人：长治医学院

  公开号：CN104610247B

  公开（公告）日：2019-03-01

  本发明公开了一种半合成紫杉烷衍生物，该衍生物对人肺腺癌细胞株A549、人乳腺癌细胞株MCF‑7、人神经胶质瘤细胞株U251、人胰腺癌细胞株PANC‑1、人结肠癌细胞株HCT116、人非小细胞肺癌细胞株H460的抗肿瘤作用试验显示有较好的抗肿瘤活性，可用于制备抗肿瘤药物。
• The Effect of the Aromatic Rings of Taxol on Biological Activity and Solution Conformation: Synthesis and Evaluation of Saturated Taxol and Taxotere Analogs
  作者：Thomas C. Boge、Richard H. Himes、David G. Vander Velde、Gunda I. Georg

  DOI：10.1021/jm00046a018

  日期：1994.9

  (triethylsilyl)baccatin III. The taxol analogue 15, in which all three taxol phenyl groups are substituted by a cyclohexyl moiety, was synthesized in one step from taxol via hydrogenation. All three analogues (9, 14, and 15) exhibited strong activity in the microtubule assembly assay and cytotoxicity comparable to taxol against B16 melanoma cells. It was also shown that 9, like taxol and taxotere, has an extended

  详细的紫杉醇和紫杉醇的新型环己基类似物的合成和生物学评价。由浆果赤霉素III通过氢化制备2-（环己基羰基）-2-脱苯甲酰基浆果赤霉素III（6）。随后将6与Nt-BOC-3-[（叔丁基二甲基甲硅烷基）氧基] -4-苯基-2-氮杂环丁酮（7）偶联，然后除去保护基，得到2-（环己基羰基）-2-脱苯甲酰基紫杉醇（ 9）。以类似的合成顺序，由N-苯甲酰基-3-[（叔丁基二甲基甲硅烷基）氧基] -4-环己基-2-氮杂环丁酮（12）和（三乙基甲硅烷基）制得3'-环己基-3'-去苯紫杉醇（14）。浆果赤霉素III。由紫杉醇经氢化一步合成了紫杉醇类似物15，其中所有三个紫杉醇苯基均被环己基部分取代。所有三个类似物（9、14，15）在微管组装试验中表现出很强的活性，并具有与紫杉醇相当的针对B16黑色素瘤细胞的细胞毒性。还显示9，像紫杉醇和紫杉醇一样，在氯仿中具有延伸的侧链，但是在DMSO /水混合物中优选采
• First synthesis and cytotoxic activity of novel docetaxel analogs modified at the C18-position
  作者：Kouichi Uoto、Ikuo Mitsui、Hirofumi Terasawa、Tsunehiko Soga

  DOI：10.1016/s0960-894x(97)10128-7

  日期：1997.12

  To investigate the effect of the C-18 position of docetaxel in its cytotoxic activity, 18-modified docetaxel analogs were synthesized for the first time from the 18-brominated baccatin derivatives. All of these analogs were found to be less active than docetaxel in cytotoxic activity against four test cell lines. (C) 1997 Elsevier Science Ltd.
• Synthesis and Antitumor Activity of Non-Prodrug Water-soluble Taxoid: 10-C-Aminoalkylated Docetaxel Analogs
  作者：Shin Iimura、Satoru Ohsuki、Jun Chiba、Kouichi Uoto、Michio Iwahana、Hirofumi Terasawa、Tsunehiko Soga

  DOI：10.3987/com-00-9051

  日期：——

  To develop non-prodrugs of taxoids possessing satisfactory stability in vivo, high water solubility and potent antitumor activity, we prepared several 10-C-sec-aminoalkylated docetaxel analogs and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines. These analogs were synthesized from a 10-deacetoxy-10-C-formylethyl baccatin derivative. Among these analogs, the 10-C-morpholinoethyl and 10-C-morpholinomethyl analogs exhibited cytotoxicity comparable or superior to that of docetaxel.
• New highly active taxoids from 9β-dihydrobaccatin-9,10-acetals. Part 2
  作者：Takashi Ishiyama、Shin Iimura、Toshiharu Yoshino、Jun Chiba、Kouichi Uoto、Hirofumi Terasawa、Tsunehiko Soga

  DOI：10.1016/s0960-894x(02)00628-5

  日期：2002.10

  To investigate structure-activity relationships of the 9,10-acetal-9beta-dihydro taxoids, we modified the 7-hydroxyl groups of the 9,10-acetonide-3'-(4-pyridyl) analogue to deoxy, methoxy, alpha-F, and 7beta,8beta-methano group. As a result of this study, we found that the 7-deoxy analogue was the strongest among these analogues. In addition, we found that the 7-deoxy-3'-(4-pyridyl) and 7-deoxy-3'-(2-pyridyl) analogues showed stronger activity against cell lines expressing P-glycoprotein than the corresponding 3'-phenyl analogue. (C) 2002 Elsevier Science Ltd. All rights reserved.