4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one | 50405-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one
• 英文别名: 4-hydroxy-3,5,6-trimethyl-2H-pyrane-2-on；4-hydroxy-3,5,6-trimethyl-2-pyrone；4-hydroxy-3,5,6-trimethylpyran-2-one；3,5,6-Trimethyl-4-hydroxy-2-pyron；3,5,6-trimethyl-4-hydroxypyrone
• CAS: 50405-44-2
• 化学式: C₈H₁₀O₃
• 分子量: 154.166
• InChiKey: ZCLDVNJXGNOJKY-UHFFFAOYSA-N

物化性质

• 沸点：
  251.6±40.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one 在 calcium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 99.0h， 生成 2-[2-hydroxy-7-phenoxyheptyl]-6-methoxy-3,5-dimethyl-4H-pyran-4-one
  参考文献：
  名称：

  Synthesis and evaluation of verticipyrone analogues as mitochondrial complex I inhibitors

  摘要：

  Verticipyrone has recently been isolated from the culture broth of Verticillium sp. and shown to inhibit NADH fumarate reductase, as well as NADH oxidoreductase ( complex I) of the mitochondrial electron transport chain. In order to assess the structural elements in verticipyrone essential for complex I inhibitor, 15 structural analogues were prepared and analyzed for their effects on mitochondrial NADH oxidoreductase and NADH oxidase activities. Also measured were the abilities of several of the analogues to inhibit respiration as judged by a shift to glycolysis, and to inhibit the growth of several mammalian cell lines. The nature of the pyrone ring was shown to be important to potency of inhibition, as was the length and nature of substituents in the side chain of the analogues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.070
• 作为产物：
  描述：

  2-methyl-3-ketobutyric acid-N-acetylcysteamine thioester 在 thioesterase 、 nanchangmycin synthase module 2 、 甲基丙二酰-辅酶A 作用下， 生成 4-hydroxy-3,5,6-trimethyl-2H-pyran-2-one
  参考文献：
  名称：

  Essential Role of the Donor Acyl Carrier Protein in Stereoselective Chain Translocation to a Fully Reducing Module of the Nanchangmycin Polyketide Synthase

  摘要：

  Incubation of recombinant module 2 of the polyether nanchangmycin synthase (NANS), carrying an appended thioesterase domain, with the ACP-bound substrate (2RS)-2-methyl-3-ketobutyryl-NANS_ACP1 (2-ACP1) and methylmalonyl-CoA in the presence of NADPH gave diastereomerically pure (25,4R)-2,4-dimethyl-5-ketohexanoic acid (4a). These results contrast with the previously reported weak discrimination by NANS module 2+TE between the enantiomers of the corresponding N-acetylcysteamine-conjugated substrate analogue (+/-)-2-methyl-3-ketobutyryl-SNAC (2-SNAC), which resulted in formation of a 5:3 mixture of 4a and its (2S,4S)-diastereomer 4h. Incubation of NANS module 2+TE with 2-ACP1 in the absence of NADPH gave unreduced 3,5,6-trimethyl-4-hydroxypyrone (3) with a K-cat of 4.4 +/- 0.9 min(-1) and a k(cat)/K-m of 67 min(-1) mM(-1), corresponding to a similar to 2300-fold increase compared to the k(cat)/K-m for the diffusive substrate 2-SNAC. Covalent tethering of the 2-methyl-3-ketobutyryl thioester substrate to the NANS ACP1 domain derived from the natural upstream PKS module of the nanchangmycin synthase significantly enhanced both the stereospecificity and the kinetic efficiency of the sequential polyketide chain translocation and condensation reactions catalyzed by the ketosynthase domain of NANS module 2.

  DOI：

  10.1021/bi201768v

文献信息

• Periselectivity in the aza-Diels–Alder Cycloaddition between α-Oxoketenes and <i>N</i>-(5-Pyrazolyl)imines: A Combined Experimental and Theoretical Study
  作者：Juan-Carlos Castillo、Brian Castro Agudelo、Jaime Gálvez、Yannick Carissan、Jean Rodriguez、Yoann Coquerel

  DOI：10.1021/acs.joc.0c00767

  日期：2020.6.5

  N-(5-pyrazolyl)imines as the 4π partners at their 2-azadiene moiety. In contrast, other cyclic and acyclic α-oxoketenes lead preferentially to 1,3-oxazin-4-ones, which now involves the α-oxoketenes as the 4π partners at their 1-oxadiene moiety and the N-(5-pyrazolyl)imines as the 2π partners at their C═N double bond. A computational modeling study using DFT methods allowed rationalizing this change of periselectivity:

  α-氧杂环丁烯之间的热6πaza-Diels-Alder环加成反应原位是由热诱导的2-重氮1,3-二酮的Wolff重排和N-（5-吡唑基）亚胺作为典型的富电子2-氮杂二烯产生两种不同的产物，基本上是所涉及的α-氧杂环丁烯的性质的函数。例如，环状五元α-氧杂环丁烯优先导致螺氢吡啶-4-酮，其中α-氧杂环丁烯在其C═C双键处为2π配偶体，而N-（5-吡唑基）亚胺为4π。在它们的2-氮杂二烯部分上形成伙伴。相比之下，其他环状和无环的α-氧杂环丁烯优先导致1,3-oxazin-4-ones，现在，α-氧杂环丁烯在其1 -oxadiene部分和4π伙伴中涉及4π伙伴。N-（5-吡唑基）亚胺在其C═N双键处为2π伙伴。使用DFT方法进行的计算模型研究可以合理化这种选择性的变化：螺吡喃并吡啶-4-酮的形成受热力学控制，而1,3-恶嗪-4-酮的形成受动力学控制，而在热力学上略有不利。五元环系列。还详细研究了α-氧杂环丁烯的竞争性环二聚化。
• .GAMMA.-Pyrones from Gonystylus keithii, as New Inhibitors of Parathyroid Hormone (PTH)-Induced Ca Release from Neonatal Mouse Calvaria.
  作者：Tsutomu KANAZAWA、Yuki OHKAWA、TAKASHI KUDA、Yasushi MINOBE、Tadato TANI、Makoto NISHIZAWA

  DOI：10.1248/cpb.45.1046

  日期：——

  New γ-pyrones, 9'-oxopodopyrone (3) and 8-methyl-9'-oxopodopyrone (4) were isolated from the leaves of Gonystylus keithii, along with known γ-pyrones, 10'-oxopodopyrone (1) and 8-methyl-10'-oxopodopyrone (2). These γ-pyrones markedly inhibited the bovine parathyroid hormone (PTH)-induced Ca release from neonatal mouse calvaria in vitro. It is the first time that γ-pyrones showed inhibitory effects on bone resorption, and these compounds may be seed compounds of new drugs for osteoporosis.

  从Gonystylus keithii的叶子中分离出新的γ-吡喃酮，9'-氧基呋喃酮(3)和8-甲基-9'-氧基呋喃酮(4)，以及已知的γ-吡喃酮，10'-氧基呋喃酮(1)和8-甲基-10'-氧基呋喃酮(2)。这些γ-吡喃酮显著抑制了培养的幼鼠颅骨中由牛甲状旁腺激素(PTH)诱导的钙释放。这是首次发现γ-吡喃酮对骨吸收有抑制作用，这些化合物可能是新型骨质疏松药物的种子化合物。
• FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF
  申请人：Sasaki Satoshi

  公开号：US20120220570A1

  公开（公告）日：2012-08-30

  The present invention provides a fused heterocycle derivative having a strong Smo inhibitory activity, and use thereof. Specially, the present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or salt thereof, and a medicament containing the compound or a prodrug thereof, which is an Smo inhibitor or an agent for the prophylaxis or treatment of cancer.

  本发明提供了一种具有强烈Smo抑制活性的融合杂环衍生物及其用途。特别地，本发明涉及一种由式子所表示的化合物，其中每个符号如说明书中所定义，或其盐，以及含有该化合物或其前药的药物，该药物是Smo抑制剂或预防或治疗癌症的药剂。
• The first total synthesis and structural determination of actinopyrone A
  作者：Seijiro Hosokawa、Kazuya Yokota、Keisuke Imamura、Yasuaki Suzuki、Masataka Kawarasaki、Kuniaki Tatsuta

  DOI：10.1016/j.tetlet.2006.05.028

  日期：2006.7

  Actinopyrone A (1) has been synthesized by using our developed remote stereoinduction, Kocienski olefination, Horner-Wadsworth-Emmons olefination, and reductive de-conjugation of the vinylpyrone. A concise method of O-methylation to obtain the gamma-pyrone has also been established. (c) 2006 Elsevier Ltd. All rights reserved.
• Total Synthesis and Biological Evaluation of Verticipyrone and Analogues
  作者：Hiroyuki Shimamura、Toshiaki Sunazuka、Takashi Izuhara、Tomoyasu Hirose、Kazuro Shiomi、Satoshi Ōmura

  DOI：10.1021/ol0626140

  日期：2007.1.1

  Total synthesis of verticipyrone, a novel NADH-fumarate reductase inhibitor, has been accomplished by a convergent approach using novel "Reverse Julia olefination" method. During total synthetic studies, we also prepared and evaluated several synthetic verticipyrone analogues, some of which exhibited more potent antiparasitic activity than the natural verticipyrone.