(2S,3S,4S,5R,6S)-3,4,5-Triacetoxy-6-aminooxy-tetrahydro-pyran-2-carboxylic acid methyl ester | 319926-20-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S,4S,5R,6S)-3,4,5-Triacetoxy-6-aminooxy-tetrahydro-pyran-2-carboxylic acid methyl ester
• 英文别名: 1-O-Amino-b-D-glucopyranuronic Acid 2,3,4-Triacetate Methyl Ester；methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-aminooxyoxane-2-carboxylate
• CAS: 319926-20-0
• 化学式: C₁₃H₁₉NO₁₀
• 分子量: 349.295
• InChiKey: MTKPYIDVPMCFJL-OBBGECFZSA-N

物化性质

• 沸点：
  422.0±45.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  150
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S,5R,6S)-3,4,5-Triacetoxy-6-aminooxy-tetrahydro-pyran-2-carboxylic acid methyl ester 在 sodium methylate 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 生成
  参考文献：
  名称：

  Biosynthesis and Identification of an N-Oxide/N-Glucuronide Metabolite and First Synthesis of an N-O-Glucuronide Metabolite of Lu AA21004

  摘要：

  本文描述了一种新类代谢物的生物合成及鉴定，即哌嗪N-氧化物/N-葡糖醛酸代谢物4-[2-(2,4-二甲基苯基硫基)-苯基]-1-β-d-葡糖醛酸-哌嗪1-氧化物（4）。该代谢物在接受了1-[2-(2,4-二甲基苯基硫基)-苯基]-哌嗪溴化氢盐（Lu AA21004，1）作为新型多模式抗抑郁药物治疗抑郁症的人类和动物的尿液及血浆中被发现。人类肝脏微粒体与尿苷5'-二磷酸葡糖醛酸结合，被用作体外系统，生成足够的4以进行一维和二维1H及13C NMR实验以阐明其结构。基于旋转框架Overhauser增强光谱NMR实验，哌嗪质子的距离与葡糖醛酸部分的异构质子之间的相关性大小与H-3'和H-5'质子相似，仅能通过空间近邻关系及推测的结构（4）来解释。结构类似物N-O-葡糖醛酸结合物6-{4-[2-(2,4-二甲基苯基硫基)-苯基]-哌嗪-1-氧基}-1-β-d-葡糖醛酸（3）也在来自人类和动物的生物样品中观察到，并报道了这一代谢物的首次有机合成和结构鉴定。对葡糖醛酸代谢物3和4进行β-葡糖醛酸酶处理主要获得预期的水解产物，羟胺4-[2-(2,4-二甲基苯基硫基)-苯基]-哌嗤-1-醇（2）。

  DOI：

  10.1124/dmd.111.040428
• 作为产物：
  描述：

  methyl 1,2,3,4-tetraacetyl-α-D-glucopyranuronate 在 氢溴酸 、 四丁基硫酸氢铵 、 碳酸氢钠 、 一水合肼 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 0.33h， 生成 (2S,3S,4S,5R,6S)-3,4,5-Triacetoxy-6-aminooxy-tetrahydro-pyran-2-carboxylic acid methyl ester
  参考文献：
  名称：

  The synthesis of the glucuronide adduct of Trocade™

  摘要：

  The synthetic preparation of the glucuronide adduct of Trocade(TM), a selective inhibitor of the MMP collagenase, is described. This was achieved by preparation of the protected O-glucuronsyl hydroxylamine (9) and subsequent coupling to the available carboxylic acid (7), followed by deprotection. The synthetic material was identical to authentic isolated metabolite, which confirmed that glucuronidation of Trocade(TM) occurs on the oxygen of the hydroxamic acid. (C) 2000 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(00)01556-2

文献信息

• Synthesis and biological evaluation of the suberoylanilide hydroxamic acid (SAHA) β-glucuronide and β-galactoside for application in selective prodrug chemotherapy
  作者：Mickaël Thomas、Freddy Rivault、Isabelle Tranoy-Opalinski、Joëlle Roche、Jean-Pierre Gesson、Sébastien Papot

  DOI：10.1016/j.bmcl.2006.11.042

  日期：2007.2

  The beta-O-glucuronide and beta-O-galactoside of SAHA have been prepared and evaluated as prodrugs for selective cancer chemotherapy (ADEPT, PMT). These new compounds are stable under physiological conditions and do not exhibit any antiproliferative activity compared to the parent drug after a 48-h treatment of H661 cells. The glucuronide derivative did not lead to the release of the drug in the presence of either Escherichia coli or bovine liver beta-glucuronidase. On the other hand, under enzymatic cleavage of galactoside prodrug by the corresponding enzyme, a rapid release of SARA was observed demonstrating that the beta-O-galactoside of SAHA is a promising candidate for in vivo investigations. (c) 2006 Elsevier Ltd. All rights reserved.
• ANTIBODY DRUG CONJUGATES COMPRISING TOXINS WITH POLAR GROUPS AND USES THEREOF
  申请人：IntoCell, Inc.

  公开号：US20230190939A1

  公开（公告）日：2023-06-22

  The present disclosure is directed toward drugs and toxins functionalized by at least one saccharide, sulfate or sulfonate; drug conjugates comprising said drugs or toxins and a cleavable linker; and targeted conjugates comprising said drugs or toxins, cleavable linkers, and targeting moieties. The present disclosure also relates to methods of treating cancers, auto-immune diseases, and inflammatory diseases using the compounds and conjugates of the disclosure.