(3R,4S)-3-hydroxy-1-(4-methoxyphenyl)-4-(2-methylprop-1-enyl)azetidin-2-one | 201044-87-3

• 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-hydroxy-1-(4-methoxyphenyl)-4-(2-methylprop-1-enyl)azetidin-2-one
• CAS: 201044-87-3
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: OQIXFZXAFKBHND-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R,4S)-3-hydroxy-1-(4-methoxyphenyl)-4-(2-methylprop-1-enyl)azetidin-2-one 在 4-二甲氨基吡啶 、 ammonium cerium(IV) nitrate 、 diethylzinc 、 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 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
• 作为产物：
  描述：

  (3R,4S)-1-p-methoxyphenyl-3-triisopropylsiloxy-4-(2-methyl-1-propenyl)azetidin-2-one 在 氢氟酸 作用下， 以 吡啶 为溶剂， 以94%的产率得到(3R,4S)-3-hydroxy-1-(4-methoxyphenyl)-4-(2-methylprop-1-enyl)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 biological evaluation of novel 3′-difluorovinyl taxoids
  作者：Larissa Kuznetsova、Liang Sun、Jin Chen、Xianrui Zhao、Joshua Seitz、Manisha Das、Yuan Li、Jean M. Veith、Paula Pera、Ralph J. Bernacki、Shujun Xia、Susan B. Horwitz、Iwao Ojima

  DOI：10.1016/j.jfluchem.2012.07.007

  日期：2012.11

  3′-difluorovinyl taxoids evaluated, eight taxoids exhibited less than 100 pM IC50 values against MCF7 cell line. Difluorovinyl taxoids induced GTP-independent tubulin polymerization much faster than paclitaxel. Then, the resulting microtubules were stable to Ca2+-induced depolymerization, indicating strong stabilization of microtubules. Molecular modeling study indicated that a difluorovinyl taxoid binds to

  一系列具有 C10 修饰以及具有 C2 和 C10 修饰的 3'-二氟乙烯基紫杉醇被战略性地设计为阻断细胞色素 P-450 3A4 酶的代谢并合成。评估了这些新型二氟乙烯基紫杉素对药物敏感的人乳腺 (MCF7)、多药耐药 (MDR) 人卵巢 (NCI/ADR)、人结肠 (HT-29) 和人胰腺 (PANC-1) 癌细胞的细胞毒性线。与紫杉醇相比，3'-二氟乙烯基紫杉醇对 MCF7、HT-29 和 PANC-1 细胞系的活性高出数倍至 16 倍，对 NCI/ADR 细胞系的效力高出三个数量级。构效关系研究表明 C2 修饰对 MDR 癌细胞系的活性至关重要，而 C10 修饰对效力的影响相当小，但有一些例外。C2 修饰对 MCF7 细胞系效力的影响按以下顺序增加：H < F < Cl < N3 . 在评估的 25 种 3'-二氟乙烯基紫杉类中，8 种紫杉类对 MCF7 细胞系的pM IC 50值小于
• Trifluoromethyl- and difluoromethyl-β-lactams as useful building blocks for the synthesis of fluorinated amino acids, dipeptides, and fluoro-taxoids
  作者：Larisa Kuznetsova、Ioana Maria Ungureanu、Antonella Pepe、Ilaria Zanardi、Xinyuan Wu、Iwao Ojima

  DOI：10.1016/j.jfluchem.2003.12.001

  日期：2004.4

  Enantiopure 1-acyl-3-hydroxyl-4-CF2H-azetidin-2-ones and 1-acyl-3-hydroxy-4-CF3-azetidin-2-ones serve as versatile intermediates for the syntheses of CF2- and CF3-containing α-hydroxy-β-amino acids, dipeptides, and taxoid anticancer agents. Both enantiomers of 3-hydroxy-4-CF2H-β-lactams can be obtained in high yields through the diethylaminosulfur trifluoride (DAST) reaction of the corresponding enantiopure

  对映体纯1-酰基-3-羟基-4- CF 2 H-氮杂环丁烷-2-酮和1-酰基-3-羟基-4- CF 3 -氮杂环丁-2-酮作为多用途的中间体，用于CF的合成2 -含CF 3的α-羟基-β-氨基酸，二肽和紫杉类抗癌药。的两种对映体的3-羟基-4- CF 2 H-β内酰胺类可以以高产率通过将获得的二乙基氨基三氟化硫（DAST）的相应对映纯的，其通过制备4-甲酰基- β内酰胺的反应[2 + 2]将乙酰氧基烯酮环加成到3-甲基-2-丁烯二胺上，然后进行酶促旋光拆分和臭氧分解。（+）-3-羟基-4-CF 3 -β-内酰胺和（−）-3-羟基-4-CF 3通过将CF 3-亚胺与乙烯酮进行[2 + 2]环加成，然后进行酶促光学拆分，也可以很容易地以对映纯形式获得-β-内酰胺。描述了制备这些对映体纯的3-羟基-4-R f -β-内酰胺的实际方法及其合成应用。
• WO2007/21957
  申请人：——

  公开号：——

  公开（公告）日：——
• Syntheses and structure–activity relationships of novel 3′-difluoromethyl and 3′-trifluoromethyl-taxoids
  作者：Larissa V. Kuznetsova、Antonella Pepe、Ioana M. Ungureanu、Paula Pera、Ralph J. Bernacki、Iwao Ojima

  DOI：10.1016/j.jfluchem.2008.05.013

  日期：2008.9

  A series of novel 3'-difluoromethyl-taxoids and 3'-trifluoromethyl-taxoids with modifications at the C2 and C10 positions were synthesized and evaluated for their in vitro cytotoxicities against human breast carcinoma (MCF7-S, MCF7-R, LCC6-WT, LCC6-MDR), non-small cell lung carcinoma (H460) and colon adenocarcinoma (HT-29) cell lines. These second-generation fluoro-taxoids exhibited several times to more than 20 times better potency than paclitaxel against drug-sensitive cancer cell lines, MCF7-S, LCC6-WT. H460, and HT-29. These fluoro-taxoids also possess two orders of magnitude higher potency than paclitaxel against drug-resistant cancer cell lines, MCF7-R and LCC6-MDR. Structure-activity relationship study shows the importance of the C10 modification for increasing the activity against multidrug-resistant cancer cell lines. Effects of the C2-benzoate modifications on the potency in the 3'-difluoromethyl-taxoid series are very clear- (i.e., F < MeO < Cl < N-3), while those in the 3'-trifluoromethyl-taxoid series are less obvious. Also, different trends in the sensitivity to the C2-substitution are observed between drug-sensitive cell lines and drug-resistant cancer cell lines that overexpress efflux pumps. (c) 2008 Elsevier B.V. All rights reserved.
• [EN] GLYCOCONJUGATES<br/>[FR] GLYCOCONJUGUÉS
  申请人：[en]UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.

  公开号：WO2022081895A1

  公开（公告）日：2022-04-21

  Disclosed herein are glycoconjugates having a cell-binding agent, such as an antibody, conjugating to a payload, such as a drug. The drug is conjugated to the cell-binding agent through an oligosaccharide linker. The glycoconjugates conjugated through the oligosaccharide linkers disclosed herein exhibit improved properties over prior glycoconjugates.