(3R,4R,5S)-5-carboxypiperidine-3,4-diol | 177567-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3R,4R,5S)-5-carboxypiperidine-3,4-diol
• 英文别名: (3S,4R,5R)-3-carboxypiperidine-4,5-diol；(3S,4R,5R)-4,5-dihydroxypiperidine-3-carboxylic Acid
• CAS: 177567-98-5
• 化学式: C₆H₁₁NO₄
• 分子量: 161.158
• InChiKey: SSMLJUWXZFXWSF-VPENINKCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.9
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  丙醛 、 (3R,4R,5S)-5-carboxypiperidine-3,4-diol 在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 以37 %的产率得到(3S,4R,5R)-4,5-dihydroxy-1-propylpiperidine-3-carboxylic acid
  参考文献：
  名称：

  Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes

  摘要：

  Selective inhibitors of gut bacterial beta-glucuronidases (GUSs) are of particular interest in the prevention of xenobiotic-induced toxicities. This study reports the first structure-activity relationships on potency and selectivity of several iminocyclitols (2-7) for the GUSs. Complex structures of Ruminococcus gnavus GUS with 2-7 explained how charge, conformation, and substituent of iminocyclitols affect their potency and selectivity. N1 of uronic isofagomine (2) made strong electrostatic interactions with two catalytic glutamates of GUSs, resulting in the most potent inhibition (K-i >= 11 nM). C6-propyl analogue of 2 (6) displayed 700-fold selectivity for opportunistic bacterial GUSs (K-i = 74 nM for E. coli GUS and 51.8 mu M for RgGUS). In comparison with 2, there was 200-fold enhancement in the selectivity, which was attributed to differential interactions between the propyl group and loop 5 residues of the GUSs. The results provide useful insights to develop potent and selective inhibitors for undesired GUSs.

  DOI：

  10.1021/acs.jmedchem.9b01918
• 作为产物：
  描述：

  烟酸甲酯 在 铂 盐酸 、 2-乙胺吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 jones reagent 、 三氟甲磺酸三甲基硅酯 、 N-甲基麻黄碱 、 硼烷 、 双氧水 、 氧气 、 sodium acetate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 18.0h， 生成 (3R,4R,5S)-5-carboxypiperidine-3,4-diol
  参考文献：
  名称：

  Selective Fowler Reductions:  Asymmetric Total Syntheses of Isofagomine and Other 1-Azasugars from Methyl Nicotinate

  摘要：

  [GRAPHICS]An efficient, high-yielding strategy has been developed for the asymmetric synthesis of 1-N-iminosugars (1-azasugars), a new class of glycosidase inhibitors with promising biomedical applications. A highly regioselective procedure for the 1,2-reduction of substituted pyridines was employed to transform methyl nicotinate into several representative 1-azasugars.

  DOI：

  10.1021/ol006810x

文献信息

• 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。
• Synthesis of a potent inhibitor of β-glucuronidase
  作者：Yasuhiro Igarashi、Mie Ichikawa、Yoshitaka Ichikawa

  DOI：10.1016/0040-4039(96)00422-4

  日期：1996.4

  A new glucuronic acid-type iminosugar in which a nitrogen atom is placed in the anomeric positon was synthesized and was proven to potently inhibit β-glucuronidase, with Ki = 79 nM.

  合成了一种新的葡萄糖醛酸型亚氨基糖，其中一个氮原子位于异位正子中，并被证明可以有效抑制β-葡萄糖醛酸苷酶，K i = 79 nM。
• Highly Selective Synthesis of 1-<i>N</i>-Iminosugars of the <scp>d</scp>-Glucose and -Glucuronic Acid Types
  作者：Yong Jip Kim、Mie Ichikawa、Yoshitaka Ichikawa

  DOI：10.1021/jo9917700

  日期：2000.4.1
• Selective Fowler Reductions:  Asymmetric Total Syntheses of Isofagomine and Other 1-Azasugars from Methyl Nicotinate
  作者：Guohua Zhao、Urmila C. Deo、Bruce Ganem

  DOI：10.1021/ol006810x

  日期：2001.1.1

  [GRAPHICS]An efficient, high-yielding strategy has been developed for the asymmetric synthesis of 1-N-iminosugars (1-azasugars), a new class of glycosidase inhibitors with promising biomedical applications. A highly regioselective procedure for the 1,2-reduction of substituted pyridines was employed to transform methyl nicotinate into several representative 1-azasugars.
• Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes
  作者：Punsaldulam Dashnyam、Hsien-Ya Lin、Chia-Yu Chen、Shijay Gao、Lun-Fu Yeh、Wei-Che Hsieh、Zhijay Tu、Chun-Hung Lin

  DOI：10.1021/acs.jmedchem.9b01918

  日期：2020.5.14

  Selective inhibitors of gut bacterial beta-glucuronidases (GUSs) are of particular interest in the prevention of xenobiotic-induced toxicities. This study reports the first structure-activity relationships on potency and selectivity of several iminocyclitols (2-7) for the GUSs. Complex structures of Ruminococcus gnavus GUS with 2-7 explained how charge, conformation, and substituent of iminocyclitols affect their potency and selectivity. N1 of uronic isofagomine (2) made strong electrostatic interactions with two catalytic glutamates of GUSs, resulting in the most potent inhibition (K-i >= 11 nM). C6-propyl analogue of 2 (6) displayed 700-fold selectivity for opportunistic bacterial GUSs (K-i = 74 nM for E. coli GUS and 51.8 mu M for RgGUS). In comparison with 2, there was 200-fold enhancement in the selectivity, which was attributed to differential interactions between the propyl group and loop 5 residues of the GUSs. The results provide useful insights to develop potent and selective inhibitors for undesired GUSs.