(3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine

• 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: (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine
• 英文别名: (3S,4S,5R)-5-(hydroxymethyl)piperidine-3,4-diol；(+)-3,4-di-epiisofagomine；D-3,4-di-epi-isofagomine
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: QPYJXFZUIJOGNX-SRQIZXRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  72.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 29.0h， 生成 (+/-)-2-[(3,4-trans-4,5-cis)-5-hydroxymethyl-3,4-dihydroxypiperidine-1-yl]ethylphosphono acid
  参考文献：
  名称：

  Synthesis and Chemistry of Noeuromycin and Isofagomine Analogues

  摘要：

  Several N-substituted analogues of noeuromycin ((2RS,3S,4R,5R)-2,3,4-trihydroxy-5 -hydroxymethylpiperidine) and isofagomine ((3R,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine) were synthesised. The isofagomine analogues (3RS,4RS,5RS)N-(2-phosphonoethyl)-3,4-dihydroxy-5-hydroxymethyl-piperidine, (3SR,4SR,5RS)-N-(2-phosphonoethyl)-3,4-dihydroxy-5-hydroxy-methylpiperidine, and (3R,4R,5R)-N-(10-chloro-9-anthracenemethyl)-3,4-dihydroxy-5-hydroxy-methylpiperidine were synthesised by direct alkylation of the corresponding azasugar. N-Substituted noeuromycin derivatives could not be made in this straightforward manner, but were made by modification of a synthesis intermediate. By this method (2RS,3S,4R,5R)-N-(4-methoxyphenyl)-2,3,4-trihydroxy-5-hydroxymethylpiperidine and (2RS,3S,4R,5R)-N-nonyl-2,3,4-trihydroxy-5-hydroxymethylpiperidine were synthesised. The stability of noeuromycin was studied and was found to depend on stereochemistry and pH. The L-fuco isomer ((2RS, 3R,4R,5R)-2,3,4-trihydroxy-5-methylpiperidine) was observed to undergo a particularly facile Amadori rearrangement at neutral pH to the 3-ketopiperidine. A noeuromycin analogue, that could not undergo the Amadori rearrangement, was synthesised.

  DOI：

  10.1081/car-200030070
• 作为产物：
  描述：

  槟榔碱 在 氢氧化钾 、 锂硼氢 、 1-氯乙基氯甲酸酯 、 三乙基硼氢化锂 、 三乙胺 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 11.58h， 生成 (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidine
  参考文献：
  名称：

  Iminosugars: potential inhibitors of liver glycogen phosphorylase

  摘要：

  The first synthesis of the single isomers (3R,4R,5R); (3S,4S,5S); (3R,4R,5S) and (3S,4S,5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported, including the synthesis of a series of N-substituted derivatives of the (3R,4R,5R)-isomer (Isofagomine). The inhibitory effect of these isomers as well as of a series of N-substituted derivatives of the (3R,4R,SR)-isomer and selected hydroxypiperidine analogues on liver glycogen phosphorylase (GP) showed that the (3R,4R,5R) configuration was essential for obtaining an inhibitory effect at submicromolar concentration. The results also showed that all three hydroxy groups should be present and could not be substituted, nor were extra OH groups allowed if sub-micromolar inhibition should be obtained. Some inhibitory effect was retained for N-substituted derivatives of Isofagagomine; however, N-substitution always resulted in a loss of activity compared to the parent compound, IC50 values ranging from 1 to 100 muM were obtained for simple alkyl, arylalkyl and benzoylmethyl substituents. Furthermore, we found that it was not enough to assure inhibitory effect to have the (R,,R) configuration. Fagomine, the (2R,3R,4R)-2-hydroxymethylpiperidine-3,4-diol analogue, showed an IC50 value of 200 muM compared to 0.7 muM for Isofagomine. In addition, Isofagomine was able to prevent basal and glucagon stimulated glycogen degradation in cultured hepatocytes with IC50 values of 2-3 muM. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00291-1

文献信息

• Asymmetrized tris(hydroxymethyl)methane as a precursor of N- and O-containing 6-membered heterocycles through ring-closing metathesis
  作者：Luca Banfi、Giuseppe Guanti、Monica Paravidino、Renata Riva

  DOI：10.1039/b502952j

  日期：——

  A novel synthetic application of asymmetrized tris(hydroxymethyl)methane (THYM*) 1, obtained in both enantiomeric forms in high e.e. via a chemoenzymatic procedure, is described. Starting from the common precursor 3, N- and O-containing 6-membered heterocycles have been prepared exploiting ring-closing metathesis as the key step. Possible elaborations of the double bond in 6 and 28 have been explored and, in the case of 28, conversion into the glycosidase inhibitor isofagomine 53 has been achieved.

  描述了一种新颖的合成应用，即不对称三（羟甲基）甲烷（THYM*）1，采用化学酶法合成获得两种对映异构体，具有较高的对映体富集度。以常见前体3为起始材料，利用环闭合重排作为关键步骤合成了含氮和含氧的六元杂环。探讨了对6和28中双键的可能改造，在28的情况下，成功转化为糖苷酶抑制剂异伐果明53。
• Synthesis of (±)-isofagomine and its stereoisomers from arecoline
  作者：Steen Uldall Hansen、Mikael Bols

  DOI：10.1039/a909472e

  日期：——

  (±)-Isofagomine (1) and all its stereoisomers were prepared in a short synthesis from arecoline. The double bond of arecoline was isomerised to be no longer conjugated to the carboxy, and the ester reduced to (hydroxymethyl)tetrahydropyridine 5 which after dihydroxylation of the alkene, separation and N-demethylation gave 1 and its isomers.

  (±)-Isofagomine (1) 及其所有立体异构体都是由异甲氧苄啶通过简短的合成方法制备的。异构化后的异胆碱双键不再与羧基共轭，酯还原成（羟甲基）四氢吡啶 5，经过烯烃二羟基化、分离和 N-去甲基化后得到 1 及其异构体。
• PARASITIC PLANT CONTROL AGENT AND PARASITIC PLANT CONTROL METHOD
  申请人：Osaka University

  公开号：EP2351484A1

  公开（公告）日：2011-08-03

  In order to provide a parasitic plant control agent and a parasitic plant control method each of which is capable of controlling a parasitic plant effectively, a parasitic plant is controlled by inhibiting gentianose metabolism in the parasitic plant so as to inhibit germination of the parasitic plant.

  为了提供一种能够有效控制寄生植物的寄生植物控制剂和寄生植物控制方法，我们通过抑制寄生植物的龙胆糖代谢来控制寄生植物，从而抑制寄生植物的发芽。
• Asymmetric Synthesis of All Stereoisomers of Isofagomine Using [2,3]-Wittig Rearrangement
  作者：Hiroki Takahata、Yukiko Mihara、Hidetomo Ojima、Tatsushi Imahori、Yuichi Yoshimura、Hidekazu Ouchi

  DOI：10.3987/com-07-s(k)58

  日期：——
• Asymmetrized tris(hydroxymethyl)methane as precursor of iminosugars: application to the synthesis of isofagomine
  作者：Giuseppe Guanti、Renata Riva

  DOI：10.1016/s0040-4039(02)02492-9

  日期：2003.1

  A new synthetic application of asymmetrized tris(hydroxymethyl)methane (THYM*), readily obtained in both enantiomeric forms through a chemoenzymatic procedure, is reported. In this case THYM* precursor 3 was elaborated by ring closing metathesis into some enantiopure branched tetrahydropyridines, that hake been used as precursors of the potent glycosidase inhibitor isofagomine 28. (C) 2002 Elsevier Science Ltd. All rights reserved.