N-丙酰基-(2S)-樟烷-10,2-磺内酰胺 | 195877-80-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: N-丙酰基-(2S)-樟烷-10,2-磺内酰胺
• 英文名称: N-propionyl-2(S)-bornane-2,10-sultam
• 英文别名: 1-[(1S,5S,7R)-10,10-dimethyl-3,3-dioxo-3lambda6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]propan-1-one；1-[(1S,5S,7R)-10,10-dimethyl-3,3-dioxo-3λ6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]propan-1-one
• CAS: 195877-80-6
• 化学式: C₁₃H₂₁NO₃S
• 分子量: 271.381
• InChiKey: JEMOGQYNLSWGPL-GBIKHYSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-碘-1-戊烯 、 N-丙酰基-(2S)-樟烷-10,2-磺内酰胺 在 sodium hexamethyldisilazane 作用下， 生成 (S)-1-((3aS,6R,7aS)-8,8-dimethyl-2,2-dioxidotetrahydro-3H-3a,6-methanobenzo[c]isothiazol-1(4H)-yl)-2-methylhept-6-en-1-one
  参考文献：
  名称：

  埃坡霉素 A 及其类似物的烯烃复分解方法

  摘要：

  描述了埃坡霉素 A (1) 和几种类似物（39-41、42-44、51-57、58-60、64-65 和 67-69）的烯烃复分解方法。关键构建块 6-8 以旋光形式构建，并通过羟醛反应和酯化偶联与烯烃复分解前体 4 偶联和加工。在 RuCl2(CHPh)(PCy3)2 的催化作用下，化合物 4 的烯烃复分解反应提供顺式和反式环烯烃 3 和 48。49 的环氧化得到埃坡霉素 A (1) 和几种类似物，而 50 的环氧化得到在额外的埃坡霉素中。异构体和更简单的中间体的类似加工导致了另一系列埃坡霉素类似物和模型系统。

  DOI：

  10.1021/ja971109i
• 作为产物：
  描述：

  丙酰氯 、 (1S)-(-)-2,10-camphorsultam 在 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 17.0h， 以73%的产率得到N-丙酰基-(2S)-樟烷-10,2-磺内酰胺
  参考文献：
  名称：

  Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency

  摘要：

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

  DOI：

  10.1021/jm9811209

文献信息

• Studies toward asymmetric synthesis of hoiamides A and B
  作者：Ming Li、Pan Han、Zhuo-Ya Mao、Wen Zhou、Chang-Mei Si、Juan Xiong、Bang-Guo Wei、Jin-Feng Hu

  DOI：10.1016/j.tetlet.2016.11.004

  日期：2016.12

  for diastereoselective synthesis of the key intermediate 5 from triheterocyclic fragment and polyketide 6 for hoiamides A (1) and B (2) was developed. The main feature is the successive construction of four stereogenic centers from C33 to C36 for hoiamides A (1) through the well-established Oppolzer’s anti-aldol and Paterson’s anti-aldol methodology. Furthermore, asymmetric allylation was also utilized

  开发了一种方便的方法，用于从三杂环片段和聚酮化合物6衍生出Hoiamides A（1）和B（2）的非对映选择性合成关键中间体5。主要特征是通过完善的Oppolzer的反醛醇缩合酶和Paterson的抗醛醇缩合法，从C33到C36连续构建四个Hoiamides A（1）立体异构中心。此外，不对称的烯丙基化也被用作关键步骤，以在C32形成hoiamides A（1）的立体中心。
• The Total Synthesis of Chondrochloren A
  作者：Yannick Linne、Elisa Bonandi、Christopher Tabet、Jan Geldsetzer、Markus Kalesse

  DOI：10.1002/anie.202016072

  日期：2021.3.22

  The first total synthesis of chondrochloren A is accomplished using a 1,2‐metallate rearrangement addition as an alternative for the Nozaki‐Hiyama‐Kishi reaction. This transformation also avoids the inherent challenges of this polyketide segment and provides a new, unprecedented strategy to assemble polyketidal frameworks. The formation of the Z‐enamide is accomplished using a Z‐selective cross coupling

  1,2-金属盐重排加成反应作为Nozaki-Hiyama-Kishi反应的替代方法，完成了软骨素A的第一个全合成。这种转变还避免了该聚酮化合物链段的固有挑战，并提供了组装聚酮化合物骨架的新的，前所未有的策略。Z-烯酰胺的形成是通过相应酰胺与Z-乙烯基溴的Z-选择性交叉偶联来完成的。
• Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency
  作者：Derek Brundish、Alice Bull、Vera Donovan、Joseph D. Fullerton、Sheila M. Garman、Judy F. Hayler、Diana Janus、Peter D. Kane、Mark McDonnell、Garrick P. Smith、Robert Wakeford、Clive V. Walker、Graham Howarth、William Hoyle、Mark C. Allen、John Ambler、Keith Butler、Mark D. Talbot

  DOI：10.1021/jm9811209

  日期：1999.11.1

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.
• The Olefin Metathesis Approach to Epothilone A and Its Analogues
  作者：K. C. Nicolaou、Y. He、D. Vourloumis、H. Vallberg、F. Roschangar、F. Sarabia、S. Ninkovic、Z. Yang、J. I. Trujillo

  DOI：10.1021/ja971109i

  日期：1997.8.1

  The olefin metathesis approach to epothilone A (1) and several analogues (39−41, 42−44, 51−57, 58−60, 64−65, and 67−69) is described. Key building blocks 6−8 were constructed in optically active form and were coupled and elaborated to olefin metathesis precursor 4 via an aldol reaction and an esterification coupling. Olefin metathesis of compound 4, under the catalytic influence of RuCl2(CHPh)(PCy3)2

  描述了埃坡霉素 A (1) 和几种类似物（39-41、42-44、51-57、58-60、64-65 和 67-69）的烯烃复分解方法。关键构建块 6-8 以旋光形式构建，并通过羟醛反应和酯化偶联与烯烃复分解前体 4 偶联和加工。在 RuCl2(CHPh)(PCy3)2 的催化作用下，化合物 4 的烯烃复分解反应提供顺式和反式环烯烃 3 和 48。49 的环氧化得到埃坡霉素 A (1) 和几种类似物，而 50 的环氧化得到在额外的埃坡霉素中。异构体和更简单的中间体的类似加工导致了另一系列埃坡霉素类似物和模型系统。