(3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-hydroxy-azepane-1-carboxylic acid tert-butyl ester

• 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: (3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-hydroxy-azepane-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3R,4R)-4-hydroxy-3-[(4-phenylmethoxybenzoyl)amino]azepane-1-carboxylate
• 化学式: C₂₅H₃₂N₂O₅
• 分子量: 440.539
• InChiKey: RPNNLQKVBQYXBD-FGZHOGPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-hydroxy-azepane-1-carboxylic acid tert-butyl ester 在 palladium dihydroxide 氢气 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 BOC-Balanol
  参考文献：
  名称：

  Total Synthesis of (-)-Balanol

  摘要：

  (-)-Balanol是一种具有强效蛋白激酶C抑制活性的真菌 metabolite，我们已通过全合成方法成功制备。该合成方法采用了阴离子同系Fries重排策略来构建苯丙酮（benzophenone）部分，同时将叠氮（azepane）部分由(2S,3R)-3-羟基赖氨酸（3-hydroxylysine）获取。

  DOI：

  10.1021/jo00097a014
• 作为产物：
  描述：

  N-BOC-GAMMA-氨基丁酸 在 palladium on activated charcoal sodium tetrahydroborate 、 CODRu(2-methylallyl)2 、 potassium tert-butylate 、 氢气 、 对甲苯磺酸 、 (R)-(+)-(6,6′-二甲氧联苯-2,2′-二基)双(二苯基膦) 、 三乙胺 、 N,N'-羰基二咪唑 、 calcium chloride 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 丙酮 为溶剂， 50.0 ℃ 、13.0 MPa 条件下， 反应 117.33h， 生成 (3R,4R)-3-(4-Benzyloxy-benzoylamino)-4-hydroxy-azepane-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  An Efficient Formal Synthesis of (−)-Balanol by Using Ruthenium-Catalyzed Asymmetric Hydrogenation

  摘要：

  An efficient formal synthesis of (-)-balanol is reported. The ten-step sequence leading to a key precursor 4 features a highly stereoselective synthesis of the functionalized hexahydroazepine core through dynamic kinetic resolution of a racemic alpha -amido beta -keto ester using a ruthenium(II)-catalyzed hydrogenation reaction.

  DOI：

  10.1002/1099-0690(200012)2000:23<3903::aid-ejoc3903>3.0.co;2-q

文献信息

• Total Synthesis of (-)-Balanol
  作者：Hideto Miyabe、Mayumi Torieda、Toshiko Kiguchi、Takeaki Naito

  DOI：10.1055/s-1997-3236

  日期：1997.5

  cyclization of 2b was found to be particularly successful in the selective synthesis of the seven-membered trans-amino alcohol 8b. Preparation of the enantiomerically pure hexahydroazepine-containing fragment was achieved through the enantioselective enzymatic acetylation of racemic alcohol 9, employing the immobilized lipase from Pseudomonas sp. The benzophenone fragment was prepared in short steps through

  描述了 (-)-balanol 的有效全合成，这是一种有效的蛋白激酶 C 抑制剂。(-)-Balanol 由一个手性含六氢氮杂的片段和一个二苯甲酮片段组成，两者都是通过新的合成路线制备的。通过 Bu3SnH 或 SmI2 促进的与甲酰基连接的肟醚 2ab 的自由基环化，以外消旋形式制备六氢吖庚因片段。发现 SmI2 促进的 2b 自由基环化在选择性合成七元反式氨基醇 8b 中特别成功。使用来自假单胞菌属的固定化脂肪酶，通过外消旋醇 9 的对映选择性酶促乙酰化，制备了对映异构纯的含六氢氮杂的片段。二苯甲酮片段是通过仿生氧化蒽醌环裂解，从市售天然大黄酸 15c 开始，以短步骤制备的。这种反应进行...
• A Novel and Chiral Synthesis of Both Enantiometers of trans-3-Amino-4-hydroxyhexahydroazepine, a Key Intermediate for the Synthesis of Balanol.
  作者：Takeaki NAITO、Mayumi TORIEDA、Kazumi TAJIRI、Ichiya NINOMIYA、Toshiko KIGUCHI

  DOI：10.1248/cpb.44.624

  日期：——

  Both enantiomers of the hexahydroazepine (7), key intermediates for the synthesis of (-)-balanol (1) and its enantiomer, were effectively synthesized via the shortest route involving stannyl radical cyclization of the aldehyde (4) connected with oxime ether followed by the optical resolution of the resulting azepine (7).

  六氢氮杂环庚烷（7）的两种对映体都是合成(-)-丙醇（1）及其对映体的关键中间体，它们都是通过最短的路线有效合成的，包括醛（4）与肟醚的链烷自由基环化，然后对生成的氮杂环庚烷（7）进行光学解析。
• Formal Total Synthesis of (−)-Balanol:  Concise Approach to the Hexahydroazepine Segment Based on RCM
  作者：Alois Fürstner、Oliver R. Thiel

  DOI：10.1021/jo991611g

  日期：2000.3.1

  concise synthesis of the hexahydroazepine moiety 13 of (-)-balanol 1 is described that comprises only eight steps and is distinctly shorter than all previous reported approaches to this particular compound. Sharpless epoxidation of divinylcarbinol 4 and ring closing alkene metathesis (RCM) reaction for the formation of the heterocyclic scaffold 9 constitute the key transformations of this sequence. The

  描述了（-）-balanol 1的六氢氮杂moiety部分13的简明合成，该合成仅包括八个步骤，并且明显短于所有先前报道的对该特定化合物的所有方法。二乙烯基甲醇4的无锐环氧化和用于形成杂环支架9的闭环烯烃复分解（RCM）反应构成了该序列的关键转化。最近报道的催化量的茚茚亚钌络合物18是最好的反应。此外，证明了只要施罗克的钼亚烷基络合物Mo（= NAr）（= CHCMe2Ph）[OC（Me）（CF3）2] 2（Ar = 2），即使存在叠氮基功能，RCM也可以成功进行。 （6-二异丙基苯基）用作预催化剂。
• An efficient approach for the synthesis of the hexahydroazepine segment of balanol
  作者：J.S. Yadav、Ch. Srinivas

  DOI：10.1016/s0040-4039(02)00681-0

  日期：2002.5

  An efficient approach for the synthesis of the hexahydroazepine segment of balanol is described in seven steps in a highly stereoselective manner starting from (S)-2,3-O-isopropylidine glyceraldehyde.

  从（S）-2,3- O-异丙基甘油醛开始，以高度立体选择性的方式，在七个步骤中描述了合成Balanol六氢氮杂庚烷链段的有效方法。
• Total Synthesis of (−)-Balanol
  作者：Hideto Miyabe、Mayumi Torieda、Kyoko Inoue、Kazumi Tajiri、Toshiko Kiguchi、Takeaki Naito

  DOI：10.1021/jo980208r

  日期：1998.6.1

  The efficient total synthesis of (-)-balanol, a potent inhibitor of the protein kinase C, is described. (-)-Balanol consists,of a chiral hexahydroazepine-containing fragment and a benzophenone fragment, both of which were prepared via novel synthetic routes. The hexahydroazepine fragment was prepared in racemic form through either Bu3SnH- or SmI2-promoted radical cyclization of oxime ethers 2ab intramolecularly connected with the formyl group. SmI2-promoted radical cyclization of 2b was found to be particularly successful in the selective synthesis of the seven-membered trans-amino alcohol 8b. Preparation of the enantiomerically pure hexahydroazepine-containing fragment was achieved through the enantioselective enzymatic acetylation of racemic alcohol 9, employing the immobilized lipase from Pseudomonas sp. The benzophenone fragment was prepared in short steps through a biomimetic oxidative anthraquinone ring cleavage starting from commercially available natural chrysophanic acid 15c. This reaction proceeded via [4 + 2]-cycloaddition of singlet oxygen to anthracene derivative 17c, followed by Baeyer-Villiger-type rearrangement of the resulting hydroperoxide to afford the benzophenone derivatives 22 and 23.