(1S,2R,5S,6S)-5,6-bis(benzyloxy)-2-(hydroxymethyl)cyclohex-3-enol | 1319731-21-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1S,2R,5S,6S)-5,6-bis(benzyloxy)-2-(hydroxymethyl)cyclohex-3-enol
• 英文别名: (3S,4S,5S,6R)-6-(hydroxymethyl)-3,4-dibenzyloxy-5-hydroxycyclohex-1-ene；2,3-bis-O-benzyl-D-galacto-cyclohexene；(1S,2R,5S,6S)-2-(hydroxymethyl)-5,6-bis(phenylmethoxy)cyclohex-3-en-1-ol
• CAS: 1319731-21-9
• 化学式: C₂₁H₂₄O₄
• 分子量: 340.419
• InChiKey: QCHCVMCMNUYHJZ-IVAOSVALSA-N

物化性质

• 熔点：
  101-103 °C
• 沸点：
  511.6±50.0 °C(predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2R,5S,6S)-5,6-bis(benzyloxy)-2-(hydroxymethyl)cyclohex-3-enol 在 四氧化锇 、 水 、 sodium hydride 、 N-甲基吗啉氧化物 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 、 叔丁醇 为溶剂， 反应 28.0h， 生成 (1S,2S,3S,4S,5S,6S)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)cyclohexane-1,2-diol
  参考文献：
  名称：

  Galacto-Configured Aminocyclitol Phytoceramides Are Potent in Vivo Invariant Natural Killer T Cell Stimulators

  摘要：

  A new class of a-galactosylceramide (alpha GC) nonglycosidic analogues bearing galacto-configured aminocyclitols as sugar surrogates have been obtained. The aminocyclohexane having a hydroxyl substitution pattern similar to an a-galactoside is efficiently obtained by a sequence involving Evans aldol reaction and ring-closing metathesis with a Grubbs catalyst to give a key intermediate cyclohexene, which has been converted in galacto-aminocyclohexanes that are linked through a secondary amine to a phytoceramide lipid having a cerotyl N-acyl group. Natural Killer T (NKT) cellular assays have resulted in the identification of an active compound, HS161, which has been found to promote NKT cell expansion in vitro in a similar fashion but more weakly than alpha GC. This compound stimulates the release of Interferon-gamma (IFN gamma) and Interleukin-4 (IL-4) in iNKT cell culture but with lower potency than alpha GC. The activation of Invariant Natural Killer T (iNKT) cells by this compound has been confirmed in flow cytometry experiments. Remarkably, when tested in mice, HS161 selectively induces a very strong production of IFN-gamma indicative of a potent Th1 cytokine profile. Overall, these data confirm the agonist activity of alpha GC lipid analogues having charged amino-substituted polar heads and their capacity to modulate the response arising from iNKT cell activation in vivo.

  DOI：

  10.1021/ja202610x
• 作为产物：
  描述：

  (S)-3-((2R,3S,4S,5S)-4,5-bis(benzyloxy)-3-hydroxy-2-vinylhept-6-enoyl)-4-isopropyloxazolidin-2-one 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 锂硼氢 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 (1S,2R,5S,6S)-5,6-bis(benzyloxy)-2-(hydroxymethyl)cyclohex-3-enol
  参考文献：
  名称：

  Galacto configured N-aminoaziridines: a new type of irreversible inhibitor of β-galactosidases

  摘要：

  N-氨基环氧乙烷是半乳糖苷酶的有效不可逆抑制剂。

  DOI：

  10.1039/c5ob00532a

文献信息

• Synthesis of α- and β-Galactopyranose-Configured Isomers of Cyclophellitol and Cyclophellitol Aziridine
  作者：Lianne I. Willems、Thomas J. M. Beenakker、Benjamin Murray、Berend Gagestein、Hans van den Elst、Erwin R. van Rijssel、Jeroen D. C. Codée、Wouter W. Kallemeijn、Johannes M. F. G. Aerts、Gijsbert A. van der Marel、Herman S. Overkleeft

  DOI：10.1002/ejoc.201402589

  日期：2014.9

  Cyclophellitol and cyclophellitol aziridine are potent and irreversible mechanism-based inhibitors of retaining β-glucosidases. Alterations in the configuration of these compounds can lead to irreversible inhibition of different classes of retaining glycosidases. We have recently reported on the design of a set of α-galactopyranose-configured cyclophellitol and cyclophellitol aziridine derivatives

  Cyclophellitol 和 cyclophellitol aziridine 是有效且不可逆的基于机制的保留 β-葡萄糖苷酶抑制剂。这些化合物构型的改变可导致对不同类别的保留糖苷酶的不可逆抑制。我们最近报道了一组 α-吡喃半乳糖配置的环酚醇和环酚醇氮丙啶衍生物的设计，它们抑制人类保留的 α-半乳糖苷酶。此外，我们已经展示了
• Direct Stereoselective Aziridination of Cyclohexenols with 3-Amino-2-(trifluoromethyl)quinazolin-4(3<i>H</i> )-one in the Synthesis of Cyclitol Aziridine Glycosidase Inhibitors
  作者：Marta Artola、Shirley Wouters、Sybrin P. Schröder、Casper de Boer、Yurong Chen、Rita Petracca、Adrianus M. C. H. van den Nieuwendijk、Johannes M. F. G. Aerts、Gijsbert A. van der Marel、Jeroen D. C. Codée、Herman S. Overkleeft

  DOI：10.1002/ejoc.201801703

  日期：2019.2.14

  configurational and functional isomers are powerful covalent inhibitors of retaining glycosidases, and find application in fundamental studies on glycosidases, amongst others in relation to inherited lysosomal storage disorders caused by glycosidase malfunctioning. Few direct and stereoselective aziridination methodologies are known for the synthesis of cyclophellitol aziridines. Herein, we present our studies

  环酚醇氮丙啶及其构型和功能异构体是保留糖苷酶的强大共价抑制剂，可用于糖苷酶的基础研究，其中包括与糖苷酶功能障碍引起的遗传性溶酶体贮积症相关的研究。很少有直接和立体选择性的氮丙啶化方法可用于合成环酚醇氮丙啶。在此，我们介绍了我们对各种构型和功能性环己烯醇等排体的直接 3-氨基-2-(三氟甲基)喹唑啉-4(3H)-one 介导的氮丙啶化作用范围的研究。我们证明了烯丙基或高烯丙基羟基可以通过氢键引导氮丙啶化反应，并且空间位阻在反应的非对映选择性中起着关键作用。
• Organic Dye-Sensitized Nitrene Generation: Intermolecular Aziridination of Unactivated Alkenes
  作者：Dennis Dam、Nathan R. Lagerweij、Katharina M. Janmaat、Ken Kok、Elisabeth Bouwman、Jeroen D. C. Codée

  DOI：10.1021/acs.joc.3c02709

  日期：2024.3.1

  intermediates, and several synthetic strategies for the direct aziridination of alkenes have been introduced. However, many of these strategies require an excess of activated alkene, suffer from competing side-reactions, have limited functional group tolerance, or involve precious transition metal-based catalysts. Herein, we demonstrate the direct aziridination of alkenes by combining sulfonyl azides as a triplet

  氮丙啶是重要的结构基序和中间体，并且已经介绍了几种直接进行烯烃氮丙啶化的合成策略。然而，许多这些策略需要过量的活化烯烃，遭受竞争性副反应，官能团耐受性有限，或者涉及贵重过渡金属基催化剂。在此，我们通过将磺酰叠氮化物作为三线态氮烯源与催化量的用作光敏剂的有机染料相结合，证明了烯烃的直接氮丙啶化。我们展示了磺酰叠氮化物的性质与光敏剂的三重激发态能量相结合如何影响氮丙啶化产率，并提供了一个机制原理来解释观察到的反应产率对有机染料性质的依赖性，以及磺酰叠氮试剂。优化的反应条件使得能够以烯烃作为限制试剂，对结构多样且复杂的带有各种官能团的烯烃进行氮丙啶化。
• Potent and Selective Activity-Based Probes for GH27 Human Retaining α-Galactosidases
  作者：Lianne I. Willems、Thomas J. M. Beenakker、Benjamin Murray、Saskia Scheij、Wouter W. Kallemeijn、Rolf G. Boot、Marri Verhoek、Wilma E. Donker-Koopman、Maria J. Ferraz、Erwin R. van Rijssel、Bogdan I. Florea、Jeroen D. C. Codée、Gijsbert A. van der Marel、Johannes M. F. G. Aerts、Herman S. Overkleeft

  DOI：10.1021/ja507040n

  日期：2014.8.20

  Lysosomal degradation of glycosphingolipids is mediated by the consecutive action of several glycosidases. Malfunctioning of one of these hydrolases can lead to a lysosomal storage disorder such as Fabry disease, which is caused by a deficiency in α-galactosidase A. Herein we describe the development of potent and selective activity-based probes that target retaining α-galactosidases. The fluorescently labeled aziridine-based probes 3 and 4 inhibit the two human retaining α-galactosidases αGal A and αGal B covalently and with high affinity. Moreover, they enable the visualization of the endogenous activity of both α-galactosidases in cell extracts, thereby providing a means to study the presence and location of active enzyme levels in different cell types, such as healthy cells versus those derived from Fabry patients.