methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[4-(1-hydroxybut-3-ynyl)-2-nitrophenoxy]oxane-2-carboxylate | 1352435-32-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[4-(1-hydroxybut-3-ynyl)-2-nitrophenoxy]oxane-2-carboxylate
• CAS: 1352435-32-5
• 化学式: C₂₃H₂₅NO₁₃
• 分子量: 523.45
• InChiKey: RWIXWGWJUZNNOM-KTCHSMFTSA-N

物化性质

• 沸点：
  630.9±55.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  190
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[4-(1-hydroxybut-3-ynyl)-2-nitrophenoxy]oxane-2-carboxylate 在 吡啶 、 咪唑 、 氢氟酸 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 烯丙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.67h， 生成 prop-2-enyl (2S,3S,4S,5R,6S)-6-[2-nitro-4-[1-(4-nitrophenoxy)carbonyloxybut-3-ynyl]phenoxy]-3,4,5-tris(prop-2-enoxycarbonyloxy)oxane-2-carboxylate
  参考文献：
  名称：

  Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin

  摘要：

  In this paper we describe the synthesis and biological evaluation of the first beta-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.

  DOI：

  10.1021/jm300348r
• 作为产物：
  描述：

  rac-4-(1-hydroxybut-3-yn-1-yl)-2-nitrophenol 、 乙酰溴-Alpha-D-葡萄糖酮酸甲基酯 在 1,1,4,7,10,10-六甲基三亚乙基四胺 、 silver carbonate 作用下， 以 乙腈 为溶剂， 以66%的产率得到methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[4-(1-hydroxybut-3-ynyl)-2-nitrophenoxy]oxane-2-carboxylate
  参考文献：
  名称：

  Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin

  摘要：

  In this paper we describe the synthesis and biological evaluation of the first beta-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.

  DOI：

  10.1021/jm300348r

文献信息

• Controlled Release of a Micelle Payload via Sequential Enzymatic and Bioorthogonal Reactions in Living Systems
  作者：Karine Porte、Brigitte Renoux、Elodie Péraudeau、Jonathan Clarhaut、Balkis Eddhif、Pauline Poinot、Edmond Gravel、Eric Doris、Anne Wijkhuisen、Davide Audisio、Sébastien Papot、Frédéric Taran

  DOI：10.1002/anie.201902137

  日期：2019.5.6

  A bioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click‐and‐release technology, we developed a new generation of cleavable micelles able to disassemble through a sequential enzymatic and bioorthogonal activation process. Proof‐of‐concept experiments showed that this new approach could be successfully used to deliver the substances

  探索了一种生物正交方法来按需释放纳米颗粒的含量。利用我们最近描述的点击释放技术，我们开发了新一代可裂解的胶束，可通过顺序的酶促和生物正交激活过程进行分解。概念验证实验表明，通过两种互补的靶向策略，这种新方法可以成功地用于将包裹在胶束中的物质递送到活细胞和小鼠的胶束中。
• Targeting the tumour microenvironment with an enzyme-responsive drug delivery system for the efficient therapy of breast and pancreatic cancers
  作者：Brigitte Renoux、Florian Raes、Thibaut Legigan、Elodie Péraudeau、Balkis Eddhif、Pauline Poinot、Isabelle Tranoy-Opalinski、Jérôme Alsarraf、Oleksandr Koniev、Sergii Kolodych、Stéphanie Lerondel、Alain Le Pape、Jonathan Clarhaut、Sébastien Papot

  DOI：10.1039/c7sc00472a

  日期：——

  low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug. This

  允许破坏肿瘤细胞同时保留健康组织的新型治疗策略的发展是癌症化学疗法的主要挑战之一。在这里，我们报道了一种低分子量药物传递系统的设计和抗肿瘤活性，该系统被设计用于在实体瘤的肿瘤微环境中选择性释放有效的单甲基auristatinE。静脉内给药后，该化合物通过迈克尔加成与血浆白蛋白共价结合，从而使其能够在肿瘤中被动蓄积，其中细胞外β-葡萄糖醛酸苷酶会启动药物的选择性释放。这种靶向装置可对小鼠原位三阴性乳腺和胰腺肿瘤（分别治愈了50％和33％的小鼠）产生出色的治疗效果，