(3S,4R,5R)-3,4-O-isopropylidene-3,4,5-trihydroxypiperidine | 144848-66-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3S,4R,5R)-3,4-O-isopropylidene-3,4,5-trihydroxypiperidine
• 英文别名: 2,3-O-isopropylidene-1,5-dideoxy-1,5-imino-D-ribitol；(3aS,7R,7aR)-2,2-dimethyl-3a,4,5,6,7,7a-hexahydro-[1,3]dioxolo[4,5-c]pyridin-7-ol
• CAS: 144848-66-8
• 化学式: C₈H₁₅NO₃
• 分子量: 173.212
• InChiKey: AYRVEFWNEXJRHZ-DSYKOEDSSA-N

物化性质

• 熔点：
  96-97 °C
• 沸点：
  297.7±40.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4R,5R)-3,4-O-isopropylidene-3,4,5-trihydroxypiperidine 在 水 作用下， 以 1,4-二氧六环 为溶剂， 以91%的产率得到(3R,4s,5S)-3,4,5-trihydroxy-piperidine
  参考文献：
  名称：

  N-Alkyl-, 1-C-Alkyl-, and 5-C-Alkyl-1,5-dideoxy-1,5-imino-(l)-ribitols as Galactosidase Inhibitors

  摘要：

  AbstractA series of 1,5‐dideoxy‐1,5‐imino‐(l)‐ribitol (DIR) derivatives carrying alkyl or functionalized alkyl groups were prepared and investigated as glycosidase inhibitors. These compounds were designed as simplified 4‐epi‐isofagomine (4‐epi‐IFG) mimics and were expected to behave as selective inhibitors of β‐galactosidases. All compounds were indeed found to be highly selective for β‐galactosidases versus α‐glycosidases, as they generally did not inhibit coffee bean α‐galactosidase or other α‐glycosidases. Some compounds were also found to be inhibitors of almond β‐glucosidase. The N‐alkyl DIR derivatives were only modest inhibitors of bovine β‐galactosidase, with IC50 values in the 30–700 μm range. Likewise, imino‐l‐ribitol substituted at the C1 position was found to be a weak inhibitor of this enzyme. In contrast, alkyl substitution at C5 resulted in enhanced β‐galactosidase inhibitory activity by a factor of up to 1000, with at least six carbon atoms in the alkyl substituent. Remarkably, the ‘pseudo‐anomeric’ configuration in this series does not appear to play a role. Human lysosomal β‐galactosidase from leukocyte lysate was, however, poorly inhibited by all iminoribitol derivatives tested (IC50 values in the 100 μm range), while 4‐epi‐IFG was a good inhibitor of this enzyme. Two compounds were evaluated as pharmacological chaperones for a GM1‐gangliosidosis cell line (R301Q mutation) and were found to enhance the mutant enzyme activity by factors up to 2.7‐fold.

  DOI：

  10.1002/cmdc.201500485
• 作为产物：
  描述：

  卡培他滨杂质25 在 palladium dihydroxide sodium azide 、 氢气 、 sodium methylate 、 对甲苯磺酸 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 39.17h， 生成 (3S,4R,5R)-3,4-O-isopropylidene-3,4,5-trihydroxypiperidine
  参考文献：
  名称：

  Synthesis of a new inhibitor of α-fucosidase

  摘要：

  A new fucose-type iminosugar in which the nitrogen is placed in the anomeric position was synthesized from D-ribose and was shown to be a potent inhibitor of alpha-fucosidase (Ki = 8.4 mu M).

  DOI：

  10.1016/0960-894x(96)00068-6

文献信息

• An efficient method for the stereoselective synthesis of bicyclic azasugars with glycosidic heteroatom
  作者：Wen Yuan、Xuelian Wei、JiajunMa、Junxiao Yang

  DOI：10.1016/j.tet.2021.132079

  日期：2021.6

  A mild and effective method for the stereoselective synthesis of bicyclic azasugars with glycosidic heteroatom isdescribed. An SN2 reaction of D-ribose tosylate with amino alcohol or diamine followed by iminium formation and intramolecular N,X-acetak formation. As a result, a new class of bicyclic azasugars wherein the heteroatom is present at the glycosidic position through the intramolecular nucleophilic

  描述了一种温和有效的立体选择性合成含糖苷杂原子双环氮杂糖的方法。D-核糖甲苯磺酸盐与氨基醇或二胺的 SN2 反应，随后形成亚胺鎓和分子内 N,X-乙酰乙酸酯。结果，在没有任何催化剂的情况下，通过分子内亲核环化反应以良好的收率和优异的立体选择性获得了一类新的双环氮杂糖，其中杂原子存在于糖苷位置，并且可以进一步衍生所需的产物以获得更多作为潜在的葡萄糖苷酶抑制剂的氮杂糖的结构类型。
• 1-<i>N</i>-Iminosugars:  Potent and Selective Inhibitors of β-Glycosidases
  作者：Yoshitaka Ichikawa、Yasuhiro Igarashi、Mie Ichikawa、Yoshitomo Suhara

  DOI：10.1021/ja973443k

  日期：1998.4.1

  are both highly potent and selective for β-glycosidases. Designed on the basis of the transition-state model of the β-glucosidase reaction, these iminosugar inhibitors differ from the currently available inhibitors in possessing a nitrogen atom at the anomeric position of the pyranose ring, thereby generating a positive charge on the anomeric position rather than on the ring oxygen of the sugar. Their

  合成了一系列 1-N-亚氨基糖，以满足对高效且对 β-糖苷酶具有选择性的糖苷酶抑制剂的需求。基于β-葡萄糖苷酶反应的过渡态模型设计，这些亚氨基糖抑制剂与目前可用的抑制剂的不同之处在于在吡喃糖环的异头位置拥有一个氮原子，从而在异头位置产生正电荷而不是比在糖的环氧上。他们的合成，从容易获得的碳水化合物衍生物开始，包括 (i) 引入氨基官能团作为叠氮基，(ii) 形成具有还原胺化作用的 1-N-亚氨基吡喃糖环，以及 (iii) 立体选择性引入羟甲基或甲基，并以高度立体选择性和有效的方式完成。
• The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs
  作者：Dominik Rejman、Radek Pohl、Martin Dračínský

  DOI：10.1002/ejoc.201001610

  日期：2011.4

  An optimized method for the synthesis of an important chiral scaffold, (3S,4R,5R)-1-N-Boc-3,4-isopropylidene-3,4,5-trihydroxypiperidine, was developed. Using this intermediate, the preparation of various chiral aminodihydroxypiperidines and their transformation into a series of non-glycosidic, six-membered azanucleosides was accomplished. NMR conformation analysis of the prepared piperidine azanucleosides

  开发了一种用于合成重要手性支架 (3S,4R,5R)-1-N-Boc-3,4-isopropylidene-3,4,5-trihydroxypiperidine 的优化方法。使用该中间体，完成了各种手性氨基二羟基哌啶的制备，并将它们转化为一系列非糖苷的六元氮杂核苷。制备的哌啶氮杂核苷的 NMR 构象分析显示偏爱椅子构象，在所有情况下核碱基都固定在赤道位置。
• Di, Jie; Rajanikanth, Bandaru; Szarek, Walter A., Journal of the Chemical Society. Perkin transactions I, 1992, # 17, p. 2151 - 2154
  作者：Di, Jie、Rajanikanth, Bandaru、Szarek, Walter A.

  DOI：——

  日期：——
• [EN] NOVEL LIGANDS FOR ASIALOGLYCOPROTEIN RECEPTOR<br/>[FR] NOUVEAUX LIGANDS POUR LE RÉCEPTEUR D'ASIALOGLYCOPROTÉINE
  申请人：SANOFI SA

  公开号：WO2022084331A3

  公开（公告）日：2022-06-02