N-benzyl-4-hydroxy-3-(4-benzyloxybenzamido)azepane

• 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: N-benzyl-4-hydroxy-3-(4-benzyloxybenzamido)azepane
• 英文别名: N-[(3S,4S)-1-benzyl-4-hydroxyazepan-3-yl]-4-phenylmethoxybenzamide
• 化学式: C₂₇H₃₀N₂O₃
• 分子量: 430.547
• InChiKey: UTAMDSHXFLNCGA-UIOOFZCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyl-4-hydroxy-3-(4-benzyloxybenzamido)azepane 在 palladium hydroxide - carbon 4-二甲氨基吡啶 、 草酰氯 、 氢气 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 反应 34.0h， 生成 (3S,4S)-balanol
  参考文献：
  名称：

  Total Synthesis of (−)- and (+)-Balanol¹

  摘要：

  Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of(2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic home-Fries rearrangement.

  DOI：

  10.1021/jo952280k
• 作为产物：
  描述：

  己内酰胺 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium hydroxide 、 四氧化锇 、 lithium aluminium tetrahydride 、 sodium azide 、 三氟甲磺酸酐 、 三氟化硼乙醚 、 水 、 双氧水 、 苄基三甲基溴化铵 、 sodium hydride 、 sodium carbonate 、 N-甲基吗啉氧化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 丙酮 、 paraffin 、 叔丁醇 为溶剂， 反应 96.5h， 生成 N-benzyl-4-hydroxy-3-(4-benzyloxybenzamido)azepane
  参考文献：
  名称：

  Total Synthesis of (−)- and (+)-Balanol¹

  摘要：

  Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of(2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic home-Fries rearrangement.

  DOI：

  10.1021/jo952280k

文献信息

• New Options for the Reactivity of the Burgess Reagent with Epoxides in Both Racemic and Chiral Auxiliary Modes - Structural and Mechanistic Revisions, Computational Studies, and Application to Synthesis
  作者：Hannes Leisch、Bradford Sullivan、Branden Fonovic、Travis Dudding、Tomas Hudlicky

  DOI：10.1002/ejoc.200900159

  日期：2009.6

  reagent with epoxides yields diastereomeric pairs of sulfamidates, which lead to cis and trans amino alcohols in each enantiomeric series. Experimental and spectral details are provided for all new sulfamidates and the products derived from them. Structure revisions have been made for several previously reported products from the reactions of the Burgess reagent with cyclic oxiranes and styrene diols.

  Burgess 试剂的手性辅助形式与环氧化物的反应产生氨基磺酸盐的非对映体对，这导致每个对映体系列中的顺式和反式氨基醇。提供了所有新磺胺酯及其衍生产品的实验和光谱细节。Burgess 试剂与环状环氧乙烷和苯乙烯二醇反应的几种先前报道的产物已经进行了结构修正。还建议对伯吉斯试剂与 1,2-二醇和环氧化物反应的可能机制进行相当大的修改。最后，包括对非手性形式的 Burgess 试剂与环氧乙烷相互作用的密度泛函理论 (DFT) 研究，以及对在使用 C2 对称催化剂的催化模式下进行的反应中观察到的缺乏不对称诱导的解释。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• Formal total synthesis of (–)- and (+)-balanol: two complementary enantiodivergent routes from vinyloxiranes and vinylaziridines
  作者：Jacqueline Gilmet、Bradford Sullivan、Tomas Hudlicky

  DOI：10.1016/j.tet.2008.10.070

  日期：2009.1

  Formal total syntheses of both enantiomers of balanol have been achieved by the preparation of the protected hexahydroazepine core 2. Two complementary routes have been investigated. The first relied on the regioselective opening of 1,2-epoxycyclohex-3-ene with a chiral-auxiliary version of the Burgess reagent to provide a diastereomeric pair of cis-fused cyclic sulfamidates. The sulfamidates were

  通过制备受保护的六氢氮杂core核2，已实现了Balanol的两种对映异构体的正式全部合成。已经研究了两种互补的途径。第一个依靠手性辅助形式的Burgess试剂对1,2-环氧环己-3-烯的区域选择性开放，以提供非对映异构体对的顺式稠合环状氨基磺酸酯。用苯甲酸铵将氨基磺酸盐转化为反式氨基苯甲酸酯，并且在分离后，通过氧化裂解和还原胺化将其转化为（-）- 2和（+）- 2。第二种方法是使用由1-溴-2,3-二羟基环己-4,6-二烯衍生的乙烯基氮丙啶，后者是通过对溴苯进行全细胞发酵而获得的。大肠杆菌JM109（pDTG601）。氮丙啶的立体选择性开放产生了必需的反式-氨基醇衍生物，其在乙烯基溴部分饱和后通过顺式-二醇的氧化裂解和还原性胺化而转化为（-）- 2和（+）- 2。提供了所有新化合物的实验数据和光谱数据。
• Synthesis and Protein Kinase Inhibitory Activity of Balanol Analogues with Modified Benzophenone Subunits
  作者：John W. Lampe、Christopher K. Biggers、Jean M. Defauw、Robert J. Foglesong、Steven E. Hall、Julia M. Heerding、Sean P. Hollinshead、Hong Hu、Philip F. Hughes、G. Erik Jagdmann、Mary George Johnson、Yen-Shi Lai、Christopher T. Lowden、Michael P. Lynch、José S. Mendoza、Marcia M. Murphy、Joseph W. Wilson、Lawrence M. Ballas、Kiyomi Carter、James W. Darges、Jefferson E. Davis、Frederick R. Hubbard、Mark L. Stamper

  DOI：10.1021/jm020018f

  日期：2002.6.1

  A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure - activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.
• BALANOIDS
  申请人：SPHINX PHARMACEUTICALS CORPORATION

  公开号：EP0687249A1

  公开（公告）日：1995-12-20
• [EN] BALANOIDS<br/>[FR] BALANOIDES
  申请人：——

  公开号：WO1994020062A2

  公开（公告）日：1994-09-15

  [EN] A novel class of therapeutic compounds, denominated Balanoids, is disclosed. Balanoids have protein kinase C inhibitory activity and selectivity among the isoforms of protein kinase C. Balanoids are useful for treatment of diseases related to protein kinase C in animals, especially humans and is especially indicated for treatment of inflammatory diseases.
  [FR] Nouvelle classe de composés thérapeutiques nommés balanoïdes. Lesdits composés possèdent une activité inhibitrice de la protéine kinase C et une sélectivité parmi les isoformes de la protéine kinase C. Les balanoïdes sont utiles pour traiter les maladies liées à la protéine kinase C chez les animaux, en particulier chez leshumains, et ils sont particulièrement indiqués pour traiter les maladies inflammatoires.