(R)-4-hydroxytetrahydro-2H-pyran-2-one | 61892-56-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (R)-4-hydroxytetrahydro-2H-pyran-2-one
• 英文别名: (4R)-4-hydroxyoxan-2-one
• CAS: 61892-56-6
• 化学式: C₅H₈O₃
• 分子量: 116.117
• InChiKey: WMHRYMDGHQIARA-SCSAIBSYSA-N

物化性质

• 沸点：
  295.8±23.0 °C(Predicted)
• 密度：
  1.276±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-hydroxytetrahydro-2H-pyran-2-one 在 sodium hydroxide 作用下， 生成
  参考文献：
  名称：

  Statin activation of skeletal ryanodine receptors (RyR1) is a class effect but separable from HMG‐CoA reductase inhibition

  摘要：

  Background and PurposeStatins, inhibitors of HMG‐CoA reductase, are mainstay treatment for hypercholesterolaemia. However, muscle pain and weakness prevent many patients from benefiting from their cardioprotective effects. We previously demonstrated that simvastatin activates skeletal ryanodine receptors (RyR1), an effect that could be important in initiating myopathy. Using a range of structurally diverse statin analogues, we examined structural features associated with RyR1 activation, aiming to identify statins lacking this property.Experimental ApproachCompounds were screened for RyR1 activity utilising [3H]ryanodine binding. Mechanistic insight into RyR1 activity was studied by incorporating RyR1 channels from sheep, mouse or rabbit skeletal muscle into bilayers.Key ResultsAll UK‐prescribed statins activated RyR1 at nanomolar concentrations. Cerivastatin, withdrawn from the market due to life‐threatening muscle‐related side effects, was more effective than currently‐prescribed statins and possessed the unique ability to open RyR1 channels independently of cytosolic Ca2+. We synthesised the one essential structural moiety that all statins must possess for HMG‐CoA reductase inhibition, the R‐3,5‐dihydroxypentanoic acid unit, and it did not activate RyR1. We also identified five analogues retaining potent HMG‐CoA reductase inhibition that inhibited RyR1 and four that lacked the ability to modulate RyR1.Conclusion and ImplicationsThat cerivastatin activates RyR1 most strongly supports the hypothesis that RyR1 activation is implicated in statin‐induced myopathy. Demonstrating that statin regulation of RyR1 and HMG‐CoA reductase are separable effects will allow the role of RyR1 in statin‐induced myopathy to be further elucidated by the tool compounds we have identified, allowing development of effective cardioprotective statins with improved patient tolerance.

  DOI：

  10.1111/bph.15893
• 作为产物：
  描述：

  (4'S)-benzyl-3'-<(3R),5-dihydroxy-pentanoyl>-oxazolidin-2'-one 在 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 48.0h， 以76%的产率得到(R)-4-hydroxytetrahydro-2H-pyran-2-one
  参考文献：
  名称：

  对苯二酚A的简化南半片段的对映选择性合成

  摘要：

  化合物2包含杀真菌的大环内酯索拉芬A 1的南半亚基。它是通过S-7的烯醇化物与内酯S-8的Meinwald反应制备的。其对映异构体和非对映异构体以类似方式合成。内酯S-8及其对映体R-8是通过三种不同的途径制备的，包括β-酮酸酯17的对映选择性催化还原。这些内酯是新的，并且潜在地用作C-5不对称结构单元。

  DOI：

  10.1016/0040-4020(95)00098-s

文献信息

• First practical asymmetric synthesis of R-(−)-and s-(+)-mevalonolactones from a single achiral precursor
  作者：Francesco Bonadies、Giovanni Rossi、Carlo Bonini

  DOI：10.1016/s0040-4039(01)91304-8

  日期：1984.1

  A new asymmetric synthesis of R-(−)- and S-(+)- mevalonolactones is described. Starting from a single achiral precursor, the synthesis proceeds by a nine-steps sequence, Sharpless epoxidation of an appropriate allylic alcohol.

  描述了R-（-）-和S-（+）-甲羟戊内酯的新的不对称合成。从一个非手性前体开始，合成过程按九步顺序进行，即适当的烯丙醇的Sharpless环氧化。
• Heterogeneous versus Homogeneous Copper(II) Catalysis in Enantioselective Conjugate-Addition Reactions of Boron in Water
  作者：Taku Kitanosono、Pengyu Xu、Shū Kobayashi

  DOI：10.1002/asia.201300997

  日期：2014.1

  reported for the conjugate addition of boron. Heterogeneous cat. 1 also gave high yields and enantioselectivities with some substrates and also gave the highest TOF (43 200 h−1) for an asymmetric conjugate‐addition reaction of boron. In addition, the catalyst systems were also applicable to the conjugate addition of boron to α,β,γ,δ‐unsaturated carbonyl compounds, although such reactions have previously

  我们已经开发了Cu II催化的硼在水中与α，β-不饱和羰基化合物和α，β，γ，δ-不饱和羰基化合物的对映体共轭加成反应。与先前报道的需要有机溶剂的Cu I催化相反，发现手性Cu II催化在水中有效地进行。已经开发了三种催化剂体系：催化剂。1：具有手性配体L 1的Cu（OH）2；猫。2：具有配体L1的Cu（OH）2和乙酸；和猫。3：具有配体L1的Cu（OAc）2。而猫。1是异构系统，猫。2和猫。3是同质系统。我们测试了27种α，β-不饱和羰基化合物和α，β-不饱和腈化合物，包括无环和环状α，β-不饱和酮，无环和环状β，β-二取代的烯酮，无环和环状α，β-不饱和酯（包括其β，β-二取代形式）和无环α，β-不饱和酰胺（包括其β，β-二取代形式）。我们找到那只猫。2和猫。图3显示了几乎所有底物的高产率和对映选择性。值得注意的是，没有报道过能以高收率和高对映选择性耐受所有这些底物的催化剂。异类猫。1
• The enantioselective synthesis of simplified southern-half fragments of soraphen A
  作者：Bernard Loubinoux、Jean-Luc Sinnes、Anthony C. O'Sullivan、Tammo Winkler

  DOI：10.1016/0040-4020(95)00098-s

  日期：1995.3

  comprises a southern-half subunit of the fungicidal macrolide soraphen A 1. It was prepared by a Meinwald reaction of the enolate of S-7 with the lactone S-8. Its enantiomer and diastereomers were synthesized in a similar manner. The lactone S-8 and its enantiomer R-8 were prepared by three different routes, including the enantioselective catalytic reduction of the β-keto ester 17. These lactones are

  化合物2包含杀真菌的大环内酯索拉芬A 1的南半亚基。它是通过S-7的烯醇化物与内酯S-8的Meinwald反应制备的。其对映异构体和非对映异构体以类似方式合成。内酯S-8及其对映体R-8是通过三种不同的途径制备的，包括β-酮酸酯17的对映选择性催化还原。这些内酯是新的，并且潜在地用作C-5不对称结构单元。
• Diastereoselective and enantioselective preparation of nor-mevaldic acid surrogates through desymmetrisation methodology. Enantioselective synthesis of (+) and (−) nor-mevalonic lactones
  作者：José Manuel Botubol-Ares、María Jesús Durán-Peña、Rosario Hernández-Galán、Isidro G. Collado、Laurence M. Harwood、Antonio J. Macías-Sánchez

  DOI：10.1016/j.tet.2015.08.010

  日期：2015.10

  Solvent-free desymmetrisation of a meso-dialdehyde with chiral alcohols, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one derivatives with a 96% de. This methodology, which yields the corresponding methyl nor-mevaldates with 99% ee, has been applied to the enantioselective synthesis of the (−)-(R) and (+)-(S) nor-mevalonic acid lactones.

  的无溶剂的去对称内消旋-dialdehyde与手性醇，导致制备的4-甲硅烷氧基-6- alkyloxytetrahydro -2- ħ -吡喃-2-酮用96％去衍生物。该方法可产生具有99％ee的相应甲基正甲羟戊酸酯，已应用于（-）-（R）和（+）-（S）甲羟戊酸内酯的对映选择性合成。
• Statin activation of skeletal ryanodine receptors (RyR1) is a class effect but separable from HMG‐CoA reductase inhibition
  作者：Chris Lindsay、Maria Musgaard、Angela J. Russell、Rebecca Sitsapesan

  DOI：10.1111/bph.15893

  日期：2022.11

  Background and PurposeStatins, inhibitors of HMG‐CoA reductase, are mainstay treatment for hypercholesterolaemia. However, muscle pain and weakness prevent many patients from benefiting from their cardioprotective effects. We previously demonstrated that simvastatin activates skeletal ryanodine receptors (RyR1), an effect that could be important in initiating myopathy. Using a range of structurally diverse statin analogues, we examined structural features associated with RyR1 activation, aiming to identify statins lacking this property.Experimental ApproachCompounds were screened for RyR1 activity utilising [3H]ryanodine binding. Mechanistic insight into RyR1 activity was studied by incorporating RyR1 channels from sheep, mouse or rabbit skeletal muscle into bilayers.Key ResultsAll UK‐prescribed statins activated RyR1 at nanomolar concentrations. Cerivastatin, withdrawn from the market due to life‐threatening muscle‐related side effects, was more effective than currently‐prescribed statins and possessed the unique ability to open RyR1 channels independently of cytosolic Ca2+. We synthesised the one essential structural moiety that all statins must possess for HMG‐CoA reductase inhibition, the R‐3,5‐dihydroxypentanoic acid unit, and it did not activate RyR1. We also identified five analogues retaining potent HMG‐CoA reductase inhibition that inhibited RyR1 and four that lacked the ability to modulate RyR1.Conclusion and ImplicationsThat cerivastatin activates RyR1 most strongly supports the hypothesis that RyR1 activation is implicated in statin‐induced myopathy. Demonstrating that statin regulation of RyR1 and HMG‐CoA reductase are separable effects will allow the role of RyR1 in statin‐induced myopathy to be further elucidated by the tool compounds we have identified, allowing development of effective cardioprotective statins with improved patient tolerance.