(3S,4R)-4-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methyl-3-piperidinol | 113225-21-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3S,4R)-4-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methyl-3-piperidinol
• 英文别名: 1-(2-Hydroxy-3-((3S,4R)-3-hydroxy-1-methylpiperidin-4-yl)-4,6-dimethoxyphenyl)ethan-1-one；1-[2-hydroxy-3-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4,6-dimethoxyphenyl]ethanone
• CAS: 113225-21-1
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: HNGILLDYMAAHTF-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  79.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methyl-3-piperidinol 在 caesium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 (3S,4R)-2-(ethylthio)-8-(3-hydroxy-1-methyl-4-piperidyl)-5,7-dimethoxy-4H-1-benzopyran-4-one
  参考文献：
  名称：

  Thio- and Oxoflavopiridols, Cyclin-Dependent Kinase 1-Selective Inhibitors:  Synthesis and Biological Effects

  摘要：

  Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC50 Of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.

  DOI：

  10.1021/jm000231g
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 生成 (3S,4R)-4-(3-acetyl-2-hydroxy-4,6-dimethoxyphenyl)-1-methyl-3-piperidinol
  参考文献：
  名称：

  摘要：

  DOI：

文献信息

• Flavone derivatives, preparation method and use as medicines
  申请人：——

  公开号：US20030119816A1

  公开（公告）日：2003-06-26

  The invention concerns novel products of formula (I) wherein: R1 represents a carbocyclic or heterocyclic radical optionally substituted; R2 and R3 are such that one represents hydrogen and the other represents piperidinyl optionally substituted; R4 represents hydrogen, alkyl or phenyl optionally substituted, said products being in all isomeric and salt forms and used as medicines.

  本发明涉及式（I）的新型产物：其中，R1代表一个可选择取代的碳环或杂环基团；R2和R3是这样的，其中一个代表氢，另一个代表可选择取代的哌啶基团；R4代表氢、烷基或苯基，可选择取代，所述产物以所有异构体和盐形式存在，并用作药物。
• STEREOSELECTIVE SYNTHESIS OF PHOSPHORUS CONTAINING ACTIVES
  申请人：ROSS BRUCE S.

  公开号：US20110245484A1

  公开（公告）日：2011-10-06

  Disclosed herein are phosphorus-containing actives, their use as actives for treating diseases, and a stereoselective process for preparing the same. Also disclosed herein are useful synthetic intermediates and processes for preparing the same.

  本文披露了含磷活性物质，其作为治疗疾病的活性物质的用途，以及用于制备它们的立体选择性过程。本文还披露了有用的合成中间体和制备它们的过程。
• METHOD FOR PRODUCING CIS-(-) FLOCINOPIPERIDOL
  申请人：SUMITOMO DAINIPPON PHARMA CO., LTD.

  公开号：US20220220072A1

  公开（公告）日：2022-07-14

  The present invention provides a method in which when using (+)-dibenzoyl-D-tartaric acid to optically divide (±)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone, an ether-based solvent is added and an extremely high yield of (R)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone (+)-dibenzoyl-D-tartrate is thereby obtained, a slurry thereof is treated with a base, a “three-dimensionally bulky reducing agent” is subsequently used, and cis-(−)-flocinopiperidol is thereby produced with surprisingly high selectivity.

  本发明提供了一种方法，当使用(+)-二苯乙酸-D-酒石酸对(±)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮进行光学分离时，加入以醚为基础的溶剂，从而得到极高收率的(R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮(+)-二苯乙酸-D-酒石酸盐，将其制成悬浮液，经过碱处理，随后使用“三维笨重还原剂”，从而以惊人的高选择性产生顺式-(−)-氟西匹啶醇。
• Stereoselective synthesis of phosphorus containing actives
  申请人：Gilead Pharmasset LLC

  公开号：EP2752422A1

  公开（公告）日：2014-07-09

  Disclosed herein is a process for preparing an enantiomerically- or a diastereomerically enriched phosphorus-containing active, salt, or pharmaceutically acceptable salt thereof, of formula I-1 , which comprises the steps of: (a) reacting a protected or unprotected Active with a base to form a salt of said active and then reacting said salt with an enantiomerically- or a diastereomerically enriched compound of formula II-1 wherein the Active is a nucleoside, a nucleoside-analog, or a non-nucleoside.

  本文公开了一种制备式 I-1 的对映体或非对映异构体富集的含磷活性物质、盐或其药学上可接受的盐的方法 ，其步骤包括(a) 使受保护或未受保护的活性物质与碱反应，形成所述活性物质的盐，然后使所述盐与富含对映体或非对映异构体的式 II-1 化合物反应； (b) 使受保护或未受保护的活性物质与碱反应，形成所述活性物质的盐，然后使所述盐与富含对映体或非对映异构体的式 II-1 化合物反应。 其中活性物质为核苷、核苷类似物或非核苷。
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  作者：

  DOI：——

  日期：——