(1R,4R,5R)-4-hydroxy-6-oxabicyclo[3.2.1]octan-7-one | 116498-92-1

• 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: (1R,4R,5R)-4-hydroxy-6-oxabicyclo[3.2.1]octan-7-one
• CAS: 116498-92-1
• 化学式: C₇H₁₀O₃
• 分子量: 142.155
• InChiKey: FJEHNJSXWDSJJG-HSUXUTPPSA-N

物化性质

• 熔点：
  163.5-165 °C
• 沸点：
  338.1±25.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 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：

  (1R,4R,5R)-4-hydroxy-6-oxabicyclo[3.2.1]octan-7-one 在 4-二甲氨基吡啶 、 2,6-二叔丁基-4-甲基吡啶 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 88.0h， 生成 methyl (1R,3R,4R)-4-[(tert-butyldimethylsilyl)oxy]-3-methoxycyclohexane-1-carboxylate
  参考文献：
  名称：

  Enantioselective synthesis of the C(18) – C(35) segment of immunosuppressant FK-506 using efficient new methodology

  摘要：

  DOI：

  10.1016/s0040-4039(01)93750-5
• 作为产物：
  描述：

  (1S,3R)-7-oxabicyclo[4.1.0]heptane-3-carboxylic acid 以 氯苯 为溶剂， 生成 (1R,4R,5R)-4-hydroxy-6-oxabicyclo[3.2.1]octan-7-one
  参考文献：
  名称：

  三羰基半缩酮的化学和埃文斯技术在免疫抑制剂 (-)-FK-506 全合成中的应用

  摘要：

  介绍了探索 FK-506 三羰基区域化学的模型研究的详细信息，并概述了它们在设计成功途径中使用这种免疫抑制剂的用途。还讨论了不对称恶唑烷酮烷基化/羟醛方法在 C 10 -C 18 片段的收敛、高度灵活的合成中的应用以及在 C 20 -C 34 片段的制备方面的改进

  DOI：

  10.1021/ja00164a023

文献信息

• Synthetic studies on the immunosuppressive agent FK-506: Enantioselective synthesis of a C22C34 fragment
  作者：Robert K. Baker、Kathleen M. Rupprecht、David M. Armistead、Joshua Boger、Robert A. Frankshun、Paul J. Hodges、Karst Hoogsteen、Judith M. Pissano、Bruce E. Witzel

  DOI：10.1016/s0040-4039(97)10532-9

  日期：1998.1

  The C28C32 cyclohexyl group of the natural product, FK-506, was prepared enantioselectively from the iodolactone by replacement of iodide with retention of configuration. The C27C28 trisubstituted olefin was introduced stereoselectively via a classical aldol/elimination sequence employing titanium enolate methodology. Elaboration of this chemistry has led to a synthesis of a C22C34 fragment of the

  天然产物FK-506的C28C32环己基是由碘内酯对映选择性制备的，方法是在保留构型的情况下替换碘化物。使用烯醇钛方法通过经典的羟醛/消除序列立体选择性地引入C27 ＝ C28三取代的烯烃。对这种化学方法的详细说明导致合成了天然产物的C22C34片段。
• Application of chemical P-450 model systems to studies on drug metabolism. Part X. Novel hydroxylactonization of γ,δ- and β,γ- unsaturated carboxylic acids with an iron porphyrin–iodosylbenzene system
  作者：Masakatsu Komuro、Tsunehiko Higuchi、Masaaki Hirobe

  DOI：10.1039/p19960002309

  日期：——

  The oxidative hydroxylactonization of γ,δ- and β,γ-unsaturated carboxylic acids by a chemical cytochrome P-450 model and rat liver microsomal systems has been investigated. In the chemical system using meso-tetrakis(2,6-dichlorphenyl)porphyrin iron chloride [Fe(TDCIPP)Cl] with iodosylbenzene (PhIO), γ,δ-unsaturated carboxylic acids have been converted into δ-hydroxy-γ-lactones in high yield and with

  研究了化学细胞色素P-450模型和大鼠肝微粒体系统对γ，δ-和β，γ-不饱和羧酸的氧化羟基活化作用。在使用内消旋-四（2,6-二氯苯基）卟啉氯化铁[Fe（TDCIPP）Cl]和碘代苯（PhIO）的化学体系中，γ，δ-不饱和羧酸已转化为δ-羟基-γ-内酯高收率和高立体选择性。作为β，γ-不饱和羧酸的实例，吲哚美辛已被转化为相应的β-羟基γ-内酯。针对内酯化机理的一些实验排除了通过环氧中间体。该产品已用作鉴定微粒体氧化中代谢物的标准品。在消炎痛的情况下，γ-内酯形式在大鼠肝微粒体系统中被检测为代谢产物，产率为1.33％。在2-二乙基氨基乙基-2,2-二戊酸戊酯盐酸盐（SKF-525A）存在下和在混合的CO-O 2（4：1）气氛下，收率显着降低。因此，这些代谢产物被认为是由细胞色素P-450依赖性反应形成的。
• Synthesis of the 9,10-acetonide of 9-dihydro-FK-506
  作者：Robert E. Ireland、Thomas K. Highsmith、Laura D. Gegnas、James L. Gleason

  DOI：10.1021/jo00045a013

  日期：1992.9

  The synthesis of the analog FKANAL (I) of the immunosuppressant FK-506 in Which the central features are the spiroenone system B which masks the alpha-allyl aldol portion of FK-506 and the spiroketal D which mimics the alpha-keto amide portion is described.
• Chlorogenic Acid and Synthetic Chlorogenic Acid Derivatives:  Novel Inhibitors of Hepatic Glucose-6-phosphate Translocase
  作者：Horst Hemmerle、Hans-Joerg Burger、Peter Below、Gerrit Schubert、Robert Rippel、Peter W. Schindler、Erich Paulus、Andreas W. Herling

  DOI：10.1021/jm9607360

  日期：1997.1.1

  The enzyme system glucose-6-phosphatase (EC 3.1.3.9) plays a major role in the homeostatic regulation of blood glucose. It is responsible for the formation of endogenous glucose originating from gluconeogenesis and glycogenolysis. Recently, chlorogenic acid was identified as a specific inhibitor of the glucose-6-phosphate translocase component (G1-6-P translocase) of this enzyme system in microsomes of rat liver. Glucose B-phosphate hydrolysis was determined in the presence of chlorogenic acid or of new synthesized derivatives in intact rat liver microsomes in order to assess the inhibitory potency of the compounds on the translocase component. Variation in the 3-position of chlorogenic acid had only poor effects on inhibitory potency. Introduction of lipohilic side chain in the 1-position led to 100-fold more potent inhibitors. Functional assays on isolated perfused rat liver with compound 29i, a representative of the more potent derivatives, showed a dose-dependent inhibition of gluconeogenesis and glycogenolyosis, suggesting glucose-6-phosphatase as the locus of interference of the compound for inhibition of hepatic glucose production also in the isolated organ model. G1-6-P translocase inhibitors may be useful for the reduction of inappropriately high rates of hepatic glucose output often found in non-insulin-dependent diabetes.
• [EN] RAPAMYCIN ANALOGUES AND THEIR PHARMACEUTICAL USE<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：ISOMERASE THERAPEUTICS LTD

  公开号：WO2015004455A3

  公开（公告）日：2015-03-12