N-tBOC-3-triisopropylsiloxy-4-phenylazetidin-2-one | 172213-23-9

• 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: N-tBOC-3-triisopropylsiloxy-4-phenylazetidin-2-one
• 英文别名: (3R,4S)-1-benzoyl-3-triisopropylsilyloxy-4-phenylazetidin-2-one；(3R,4S)-1-[(1,1-Dimethylethoxy)carbonyl]-3-triisopropylsilyloxy-4-phenyl-2-azetidinone；tert-butyl (3R,4S)-2-oxo-4-phenyl-3-tri(propan-2-yl)silyloxyazetidine-1-carboxylate
• CAS: 172213-23-9
• 化学式: C₂₃H₃₇NO₄Si
• 分子量: 419.637
• InChiKey: GYEWWADWVOWMOF-VQTJNVASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.07
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 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：

  N-tBOC-3-triisopropylsiloxy-4-phenylazetidin-2-one 在 吡啶 、 氢氟酸 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 3'-N-debenzoyl-N-tert-butoxycarbonyl-9(R)-dihydro-7,9-diacetyl-1-deoxypaclitaxel
  参考文献：
  名称：

  1-脱氧紫杉醇类似物的合成和生物学评价。

  摘要：

  天然存在的紫杉醇浆果赤霉素VI已通过选择性脱酰基，然后连接C-13侧链，转化为各种1-脱氧紫杉醇衍生物。在微管蛋白聚合和细胞毒性试验中都测定了所得类似物的生物活性，并发现了几种具有与紫杉醇相当活性的类似物。因此看来1-羟基对于紫杉醇的活性不是必需的。

  DOI：

  10.1021/jo981406l
• 作为产物：
  描述：

  N-亚苄基-4-甲氧基苯胺 在 4-二甲氨基吡啶 、 ammonium cerium(IV) nitrate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-tBOC-3-triisopropylsiloxy-4-phenylazetidin-2-one
  参考文献：
  名称：

  Structure–activity relationship study of taxoids for their ability to activate murine macrophages as well as inhibit the growth of macrophage-like cells

  摘要：

  A series of new taxoids modified at the C-3', C-3'N, C-10, C-2 and C-7 positions has been designed, synthesized and evaluated for their potency to induce NO and TNF production by peritoneal murine macrophages (Mphi) from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ strains and human blood cells, and for their ability to inhibit the growth of Mphi-like cell lines J774.1 and J7.DEF3. The SAR-study has shown that the nature of the substituents at these positions have critical effect on the induction of TNF and NO production by Mphi. Positions G-3' and C-10 are the most flexible and an intriguing effect of the length of the substituents at the C-10 position is observed for taxoids bearing a straight chain alkanoyl moiety. An aromatic group at the C-3'N and C-2 positions is required for the activity, while only hydroxyl or acetyl substituents seem to be tolerated at the C-7 position. The natural stereochemistry in the C-13 isoserine side chain of the taxoids is an absolute requirement for macrophage activation. It has also been clearly shown that there is no correlation between the ability of the taxoids to induce TNF/NO production in C3H/HeN M and the cytotoxicity against Mphi-like cells. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00181-0

文献信息

• New approaches to the asymmetric synthesis of dipeptide isosteres via β-Lactam Synthon Method
  作者：Iwao Ojima、Hong Wang、Tao Wang、Edward W. Ng

  DOI：10.1016/s0040-4039(97)10677-3

  日期：1998.2

  New and efficient synthetic routes to dipeptide isosteres with high enantiomeric purity, e.g., hydroxyethylene, dihydroxyethylene and hydroxyethylamine isosteres, have been developed via oxiranes 6 and formyloxazolines 13 derived from N-t-Boc-β-lactams 4.

  通过由N -t-Boc-β-内酰胺4衍生的肟基6和甲酰恶唑啉13，已经开发出具有高对映体纯度的二肽等排体（例如，羟乙烯，二羟乙烯和羟乙胺等排体）的新型有效合成途径。
• Synthesis and biological evaluation of novel larotaxel analogues
  作者：Sumei Ren、Yujie Wang、Junfei Wang、Dingding Gao、Minmin Zhang、Ning Ding、Yingxia Li

  DOI：10.1016/j.ejmech.2018.07.029

  日期：2018.8

  has been shown that the majority of these larotaxel analogues are exceptionally potent against both drug-sensitive tumor cells and tumor cells with drug resistance arising from P-glycoprotein over expression. Further in vivo antitumor efficacies investigations revealed A2 might be a potent antitumor drug candidate for further preclinical evaluation.

  紫杉醇是一类成功的药物，已成功用于多种癌症的化学疗法中。然而，尽管产生了这些类生物的希望和希望，但它们的效用受到一些临床限制的阻碍。在许多不同的实验室中进行了类毒素的广泛的结构-活性关系（SAR）研究。鉴于尚未进行基于新一代类毒素拉罗他赛的SAR研究。鉴于Larotaxel的临床前和临床数据优于以前的类毒素，因此设计，半合成并在Larotaxel的C3'/ C3'-N和C2位置进行了战略性修饰的新的类紫杉醇在体内的效力和功效进行了研究。体外。因此，已经表明，这些拉罗他赛类似物中的大多数对药物敏感性肿瘤细胞和由P-糖蛋白过度表达引起的耐药性的肿瘤细胞都具有异常强的作用。进一步的体内抗肿瘤功效研究表明，A2可能是进行进一步临床前评估的有效抗肿瘤药物候选物。
• Synthesis and biological evaluation of novel taxoids designed for targeted delivery to tumors
  作者：Erkan Baloglu、Michael L. Miller、Elizabeth E. Roller、Emily E. Cavanagh、Barbara A. Leece、Victor S. Goldmacher、Ravi V.J. Chari

  DOI：10.1016/j.bmcl.2004.09.025

  日期：2004.12

  they are capable of targeting tumor markers selectively. We have prepared taxoids with significantly higher cytotoxicity than paclitaxel and docetaxel. These taxoids now meet the high potency required for use in a targeted-delivery approach using monoclonal antibodies. The synthesis and biological evaluation of these taxoids are reported.

  药物-抗体缀合物的使用提供了将抗癌药物靶向递送至癌细胞的方法。单独的单克隆抗体通常不具有很高的治疗功效，但是，它们能够选择性地靶向肿瘤标志物。我们准备了比紫杉醇和多西紫杉醇具有明显更高细胞毒性的紫杉烷类药物。现在，这些类紫杉醇可满足使用单克隆抗体进行靶向递送方法所需的高效力。报告了这些类紫杉醇的合成和生物学评估。
• Synthesis and Structure−Activity Relationships of Nonaromatic Taxoids:  Effects of Alkyl and Alkenyl Ester Groups on Cytotoxicity
  作者：Iwao Ojima、Scott D. Kuduk、Paula Pera、Jean M. Veith、Ralph J. Bernacki

  DOI：10.1021/jm9606711

  日期：1997.1.1

  Several new nonaromatic taxoids are synthesized by means of the beta-lactam synthon method. These include taxoids modified with 3-methylbut-2-enoate, 3-methylbutanoate, and cyclohexanecarboxylate groups in place of the benzoate at the C-2 position. In addition, taxoids with 2-methylprop-1-enyl, 2-methylpropyl, (E)-prop-1-enyl, and cyclohexyl groups at the C-3' position are also prepared in combination with the modifications at C-2. The alkyl and alkenyl ester groups at C-2 displayed pronounced effects on the in vitro cytotoxicity. Two of the fully aliphatic taxoids possess similar or stronger activity than paclitaxel and docetaxel. It is clear that the 2-benzoate does not play a unique role, and replacement with the appropriate alkyl and alkenyl groups provides taxoids with equivalent or superior activity.
• New photoaffinity analogs of paclitaxel
  作者：Iwao Ojima、Pierre-Yves Bounaud、David G. Ahern

  DOI：10.1016/s0960-894x(99)00161-4

  日期：1999.4

  Two new photoreactive paclitaxel analogs bearing [H-3(2)]-3-(4-benzoyl)phenylpropanoyl group as the photophore as well as radiolabeling unit at the 7 and 10 positions, respectively, are developed. These new photoreactive analogs showed excellent preliminary results on the photoaffinity labeling of tubulin and P-glycoprotein. (C) 1999 Elsevier Science Ltd. All rights reserved.