(1R,2R,3S,4R,5R,6S)-5-hydroxymethyl-7-oxabicyclo<4.1.0>heptane-2,3,4-triol | 134680-56-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧杂环己烷
• 英文名称: (1R,2R,3S,4R,5R,6S)-5-hydroxymethyl-7-oxabicyclo<4.1.0>heptane-2,3,4-triol
• 英文别名: (1R,2R,3S,4R,5R,6S)-5-(hydroxymethyl)-7-oxabicyclo[4.1.0]heptane-2,3,4-triol；(1R,2R,3S,4R,5R,6S)-5-hydroxymethyl-7-oxa-bicyclo[4.1.0]heptane-2,3,4-triol；1,6-epi-cyclophellitol；1,6-epicyclophellitol；(+)-cyclophellitol
• CAS: 134680-56-1
• 化学式: C₇H₁₂O₅
• 分子量: 176.169
• InChiKey: YQLWKYQDOQEWRD-XQCVOTFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  93.4
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,2R,3S,4R,5R,6S)-5-hydroxymethyl-7-oxabicyclo<4.1.0>heptane-2,3,4-triol 在 sodium hydride 、 三苯基瞵硫 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 80.0h， 生成 cyclophellitol thiirane
  参考文献：
  名称：

  A family of cyclophellitolanalogs: Synthesis and evaluation.

  摘要：

  DOI：

  10.7164/antibiotics.46.1919
• 作为产物：
  描述：

  (1S,2R,3R,4R)-2,3-di-O-benzyl-4-benzyloxymethylcyclohex-5-ene-1,2,3-triol 在 palladium on activated charcoal 氢气 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 (1R,2R,3S,4R,5R,6S)-5-hydroxymethyl-7-oxabicyclo<4.1.0>heptane-2,3,4-triol
  参考文献：
  名称：

  Facile syntheses of cyclopnellitol and its (1R,6S)-, (1R,2S,6S)-, (2S)-diastereoisomers from (–)-quinic acid

  摘要：

  环黄柏醇及其(1R,6S)-、(1R,2S,6S)-和(2S)-非对映异构体是由奎宁酸通过区域选择性环硫酸酯开环反应、区域特异性氧化消除和环氧化反应生成的。

  DOI：

  10.1039/c39930000995

文献信息

• Exploring functional cyclophellitol analogues as human retaining beta-glucosidase inhibitors
  作者：Kah-Yee Li、Jianbing Jiang、Martin D. Witte、Wouter W. Kallemeijn、Wilma E. Donker-Koopman、Rolf G. Boot、Johannes M. F. G. Aerts、Jeroen D. C. Codée、Gijsbert A. van der Marel、Herman S. Overkleeft

  DOI：10.1039/c4ob01611d

  日期：——

  The natural product, cyclophellitol and its aziridine analogue are potent mechanism-based retaining β-glucosidase inhibitors. In this paper we explore the inhibitory potency of a number of cyclophellitol analogues against the three human retaining β-glucosidases, GBA, GBA2 and GBA3. We demonstrate that N-alkyl cyclophellitol aziridine is at least equally potent in inhibiting the enzymes evaluated as

  天然产物环丙醇及其氮丙啶类似物是有效的基于机理的保留β-葡萄糖苷酶抑制剂。在本文中，我们探索了许多环糖醇类似物对三种人类保留的β-葡萄糖苷酶GBA，GBA2和GBA3的抑制作用。我们证明，N-烷基环磷脂醇氮丙啶至少在抑制被评估为其N-酰基同类物的酶方面具有同等效力，而N-磺酰基类似物则是相当弱的抑制剂。我们的研究结果补充了有关环糖醇类似物抑制能力的文献，并为将来在生理介质中稳定探针设计出更有效的基于活性的糖苷酶探针提供了希望。
• Synthesis and Evaluation of Hydroxymethylaminocyclitols as Glycosidase Inhibitors
  作者：Ana Trapero、Meritxell Egido-Gabás、Jordi Bujons、Amadeu Llebaria

  DOI：10.1021/acs.joc.5b00133

  日期：2015.4.3

  were tested as glycosidase inhibitors. Cyclitols having an amino group in an α configuration at a position equivalent to the anomeric in the sugar were found to be low micromolar inhibitors of the α-glucosidase from baker’s yeast with Ki’s near to 2 μM. On the other hand, N-octyl aminocyclitols having the nitrogen substituents in an α or β configuration were found to be good inhibitors of recombinant

  通过立体控制环氧化物开放的环己烷环氧化物环磷脂醇和1，6-表-环磷脂醇的羟基保护形式，合成了葡萄糖的四个系列的C 7 N氨基环醇类似物。测试所得的羟甲基取代的氨基环糖醇作为糖苷酶抑制剂。发现具有与糖中的异头异构体相当的位置处具有α构型的氨基的环糖醇是来自面包酵母的K i接近2μM的低微摩尔α-葡萄糖苷酶抑制剂。另一方面，发现具有α或β构型的氮取代基的N-辛基氨基环醇是具有K i的重组β-葡萄糖脑苷脂酶的良好抑制剂。值在8.3和17μM之间，并且在低微摩尔浓度下还抑制了活细胞中的溶酶体β-葡萄糖苷酶活性。计算对接研究表明，不同系列的β-葡萄糖脑苷脂酶抑制剂之间存在差异结合。与实验结果一致，获得的结合姿势表明，在模拟底物中脂质链之一的抑制剂中，烷基脂质取代基的存在对效能至关重要。相比之下，氨基环糖醇中的羟甲基取代基与母体葡萄糖基神经酰胺的匹配似乎对于有效抑制并不是严格必要的，这表明简化糖模拟设计中结构相似性的风险。
• (–)-Quinic acid in organic synthesis. Part 4. Syntheses of cyclophellitol and its (1R, 6S)-, (2S)-, (1R, 2S, 6S)-diastereoisomers
  作者：Tony K. M. Shing、Vincent W.-F. Tai

  DOI：10.1039/p19940002017

  日期：——

  Cyclophellitol 1 and its (1R, 6S)-, (2S)-, (1R, 2S, 6S)-diastereoisomers 2, 3 and 4 are constructed from quinic acid involving the following key steps: regioselective cyclic sulfate ring opening, regiospecific oxidative elimination and an epoxidation. Diastereoisomers 1, 2, 3 and 4 are characterized as their corresponding tetraacetates 5, 6, 7 and 8.

  Cyclophellitol 1和它的（1 - [R，6小号） - ，（2小号） - ，（1 - [R，2小号，6小号）-diastereoisomers 2，3和4是从奎尼酸涉及以下主要步骤构成：区域选择性环硫酸酯开环，区域特异性氧化消除和环氧化。对映异构体1，2，3和4的特征为它们相应的四乙酸盐5，6，7和8。
• Total syntheses of glucosidase inhibitors, cyclophellitols
  作者：Kuniaki Tatsuta、Yoshihisa Niwata、Kazuo Umezawa、Kazunobu Toshima、Masaya Nakata

  DOI：10.1016/0008-6215(91)89017-a

  日期：1991.12

  A beta-D-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3 + 2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2.3,4-Tri-O-benzyl-6,7-dideoxy-D-ido-hept-6-enose (E,Z)-oxime (6) was prepared from L-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-enc (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl alpha-D-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.
• A novel chemo-multienzymatic synthesis of bioactive cyclophellitol and epi-cyclophellitol in both enantiopure forms
  作者：Nicola D’Antona、Raffaele Morrone、Paolo Bovicelli、Giovanni Gambera、David Kubáč、Ludmila Martínková

  DOI：10.1016/j.tetasy.2010.10.010

  日期：2010.10

  A new route to synthesize cyclophellitol and epi-cyclophellitol from racemic starting materials in enantiopure forms has been developed The synthesis involves a multi-enzymatic biotransformation pathway of the novel cyano-cyclitol (1R 4S 5R 6R)/(1S 4R 5S 6S)-4 5 6-trihydroxycyclohex-2-enecarbonitrile by a cooperative use of lipase nitrile hydratase and amidase (C) 2010 Elsevier Ltd All rights reserved