deoxykalafungin | 1093070-41-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异色满醌
• 英文名称: deoxykalafungin
• 英文别名: (3aR,5R,11bR)-5-methyl-3,3a-dihydro-2H-benzo[g]furo[3,2-c]isochromene-2,6,11(5H,11bH)-trione；7-deoxykalafungin；(3aR,5R,11bR)-5-methyl-3,3a,5,11b-tetrahydro-2H-benzo[g]furo[3,2-c]isochromene-2,6,11-trione；(11R,15R,17R)-17-methyl-12,16-dioxatetracyclo[8.7.0.03,8.011,15]heptadeca-1(10),3,5,7-tetraene-2,9,13-trione
• CAS: 1093070-41-7
• 化学式: C₁₆H₁₂O₅
• 分子量: 284.268
• InChiKey: CLQWEHDPSOGFQR-FJHWUWLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-<(2'R,3'R)-3'-hydroxy-5'-oxotetrahydrofuran-2'-yl>-1,4-dimethoxynaphthalene 在 boron trifluoride diethyl etherate 、 cerium ammonium nitrate 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 0.5h， 生成 deoxykalafungin
  参考文献：
  名称：

  Preparation and evaluation of deconstruction analogues of 7-deoxykalafungin as AKT kinase inhibitors

  摘要：

  The pyranonaphthoquinone (PNQ) lactone natural products, including 7-deoxykalafungin, have been reported to be potent and selective covalent inhibitors of AKT kinase. In this work we seek to identify structural features of the natural product scaffold that are essential for potency and selectivity. Using a deconstruction approach, we designed and prepared simplified analogues of 7-deoxykalafungin. Testing of the compounds for their ability to inhibit AKT and the closely related kinase PKA revealed that the 3,6-dihydro-2H-pyran ring of the PNQ lactones is required for potent and selective inhibition of AKT. We have also unexpectedly identified a new submicromolar inhibitor of PKA. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.020

文献信息

• Enantioselective synthesis of pyranonaphthoquinone antibiotics using a CBS reduction/cross-metathesis/oxa-Michael strategy
  作者：Paul A. Hume、Jonathan Sperry、Margaret A. Brimble

  DOI：10.1039/c1ob05595j

  日期：——

  dimethoxynaphthalene 13 with methyl acrylate, and (4) intramolecular oxa-Michael addition of alcohol 8 to form the core naphthopyran ring system. This novel approach delivers naphthopyrans possessing the natural trans-stereochemistry observed in the pyranonaphthoquinone family of antibiotics.

  据报道，对映选择性合成了脱氧二氢卡拉芬净（5），顺式-脱氧二氢卡拉芬净（6）和脱氧卡拉胶（7）。该策略基于以下4个关键反应：（1）CBS还原前手性酮10以在C-1处引入手性;（2）醌9a的自由基烯丙基化; （3）二甲氧基萘13与丙烯酸甲酯的交叉复分解，以及（ 4）分子内氧杂-迈克尔加成醇8形成核心萘并吡喃环系统。这种新颖的方法可提供具有吡喃并萘醌家族抗生素中所观察到的天然反式立体化学的萘并吡喃。
• Pyranonaphthoquinone Lactones: A New Class of AKT Selective Kinase Inhibitors Alkylate a Regulatory Loop Cysteine
  作者：Edward J. Salaski、Girija Krishnamurthy、Wei-Dong Ding、Ker Yu、Shabana S. Insaf、Clark Eid、Jaechul Shim、Jeremy I. Levin、Keiko Tabei、Lourdes Toral-Barza、Wei-Guo Zhang、Leonard A. McDonald、Erick Honores、Cilien Hanna、Ayako Yamashita、Bernard Johnson、Zhong Li、Leif Laakso、Dennis Powell、Tarek S. Mansour

  DOI：10.1021/jm900075g

  日期：2009.4.23

  The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined, PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.
• Direct Oxa-Pictet−Spengler Cyclization to the Natural (3a,5)-<i>trans</i>-Stereochemistry in the Syntheses of (+)-7-Deoxyfrenolicin B and (+)-7-Deoxykalafungin
  作者：Clark N. Eid、Jaechul Shim、Jack Bikker、Melissa Lin

  DOI：10.1021/jo801945n

  日期：2009.1.2

  The pyranonaphthoquinones (+)-7-deoxyfrenolicin B and (+)-7-deoxykalafungin were synthesized in four steps using an oxa-Pictet-Spengler cyclization that directly provided the natural (3a,5)-trans-substituted dihydronaphthopyrans with high diastereoselectivity. This outcome is in contrast to the unnatural (3a,5)-cis-substituted dihydronaphthopyrans reported under similar conditions for the syntheses of (+)frenolicin B and (+)-kalafungin. Computational modeling is presented that provides insight into this unusual stereoselectivity.
• Preparation and evaluation of deconstruction analogues of 7-deoxykalafungin as AKT kinase inhibitors
  作者：Sudha Korwar、Thuy Nguyen、Keith C. Ellis

  DOI：10.1016/j.bmcl.2013.11.020

  日期：2014.1

  The pyranonaphthoquinone (PNQ) lactone natural products, including 7-deoxykalafungin, have been reported to be potent and selective covalent inhibitors of AKT kinase. In this work we seek to identify structural features of the natural product scaffold that are essential for potency and selectivity. Using a deconstruction approach, we designed and prepared simplified analogues of 7-deoxykalafungin. Testing of the compounds for their ability to inhibit AKT and the closely related kinase PKA revealed that the 3,6-dihydro-2H-pyran ring of the PNQ lactones is required for potent and selective inhibition of AKT. We have also unexpectedly identified a new submicromolar inhibitor of PKA. (C) 2013 Elsevier Ltd. All rights reserved.