(3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)piperidine

• 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,5S)-3,4-dihydroxy-5-(hydroxymethyl)piperidine
• 英文别名: (3S,4S,5S)-3,4-dihydroxy-5-hydroxymethylpiperidine；(3S,4S,5S)-5-(Hydroxymethyl)piperidine-3,4-diol；(-)-isofagomine；L-isofagomine
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: QPYJXFZUIJOGNX-ZLUOBGJFSA-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,5S)-3,4-dihydroxy-5-(hydroxymethyl)piperidine 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-trans)-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 7.58h， 生成 (3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)piperidine
  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

• Acceleration effect of allylic hydroxy group on ring-closing enyne metathesis of terminal alkynes: scope and application to the synthesis of isofagomine
  作者：Tatsushi Imahori、Hidetomo Ojima、Hiroki Tateyama、Yukiko Mihara、Hiroki Takahata

  DOI：10.1016/j.tetlet.2007.11.098

  日期：2008.1

  substituent effect on ring-closing enyne metathesis has been found. An allylic hydroxy group on enyne substrates accelerates ring-closing enyne metathesis of terminal alkynes. The reaction proceeds smoothly without ethylene atmosphere and/or more reactive newer generation Ru-carbene catalysts, which are generally necessary to promote the reaction. This efficient reaction was applied to the synthesis of

  已经发现了对闭环烯炔复分解的有趣的烯丙基取代基作用。烯炔底物上的烯丙基羟基可促进末端炔烃的闭环烯炔复分解。该反应在没有乙烯气氛和/或反应性更高的新一代Ru-卡宾催化剂的情况下顺利进行，而这通常是促进反应所必需的。将该有效反应应用于异黄酮的合成。
• A Novel Approach to Both the Enantiomers of Potent Glycosidase Inhibitor Isofagomine via PET-Promoted Cyclization of 1-[Benzyl(trimethylsilyl-methyl)amino]-1,4,5-trideoxy-2,3-<b><i>O</i></b>-(1-methylethylidene)-<b><i>threo</i></b>-pent-4-ynitol
  作者：Ganesh Pandey、Manmohan Kapur

  DOI：10.1055/s-2001-15063

  日期：——

  The cyclization of PET-generated α-trimethylsilylmethylamine radical cation to a tethered acetylene moiety has been exploited to solve the problem of the generation of an aminomethyl group next to a stereocenter in the synthesis of 1-N-iminosugar type glycosidase inhibitors. Its success is demonstrated by the synthesis of (+)- as well as (-)-isofagomine, an extremely potent β-glucosidase inhibitor of the 1-N-iminosugar class.

  在合成 1-N-iminosugar 型糖苷酶抑制剂时，利用 PET 生成的δ-三甲基硅甲胺自由基阳离子环化到系链炔基的方法解决了在立体中心旁生成氨基甲基的问题。(+)- 和 (-)-isofagomine 的合成证明了这一方法的成功，isofagomine 是一种极其有效的 1-N-iminosugar 类δ-糖苷酶抑制剂。
• A New Route to Diverse 1-Azasugars from <i>N</i>-Boc-5-hydroxy-3-piperidene as a Common Building Block
  作者：Hidekazu Ouchi、Yukiko Mihara、Hiroki Takahata

  DOI：10.1021/jo050519j

  日期：2005.6.1

  for the synthesis of a variety of 1-azasugars with a nitrogen atom at the anomeric position is described. The readily available chiral N-Boc-5-hydroxy-3-piperidene 3 is transformed to isofagomine (2), homoisofagomine (13), and 5‘-deoxyisofagomine (14) via stereoselective epoxidation and regioselective ring-cleavage in a highly stereocontrolled manner. In addition, the synthesis of all four stereoisomers

  描述了一种合成具有异头位置氮原子的各种1-氮杂双胍的新的通用方法。易于获得的手性N -Boc-5-羟基-3-哌啶3通过立体选择性环氧化和区域选择性环裂解，以高度立体可控的方式转化为异黄花碱（2），高异黄花碱（13）和5'-脱氧异黄花碱（14）。 。此外，3,4,5- trihydroxypiperidines（所有四种立体异构体的合成18 - 21）被划分为1-azasugar型葡糖苷酶抑制剂是立体选择性地从（手性）啶实现3。
• 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。
• A short and concise synthesis of isofagomine, homoisofagomine, and 5′-deoxyisofagomine
  作者：Hidekazu Ouchi、Yukiko Mihara、Hitomi Watanabe、Hiroki Takahata

  DOI：10.1016/j.tetlet.2004.07.127

  日期：2004.9

  A short and concise synthesis of isofagomine derivatives via the epoxidation of chiral N-Boc-5-hydroxy-3-piperidene, followed by regioselective epoxide ring opening is described. This constitutes the first reported synthesis of homoisofagomine and the 5'-deoxyisofagomine. (C) 2004 Elsevier Ltd. All rights reserved.