(2S,5S)-9-Benzyloxy-5-hydroxymethyl-2-isopropyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one | 215300-61-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,5S)-9-Benzyloxy-5-hydroxymethyl-2-isopropyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one
• 英文别名: (2S,5S)-5-(hydroxymethyl)-9-phenylmethoxy-2-propan-2-yl-2,4,5,6-tetrahydro-1H-1,4-benzodiazocin-3-one
• CAS: 215300-61-1
• 化学式: C₂₁H₂₆N₂O₃
• 分子量: 354.449
• InChiKey: KNPXSKFGVOTDGX-PXNSSMCTSA-N

物化性质

• 沸点：
  602.6±55.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,5S)-9-Benzyloxy-5-hydroxymethyl-2-isopropyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium on activated charcoal 、 copper(l) iodide 咪唑 、 氢气 、 四丁基碘化铵 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 51.67h， 生成 (S,S)-9-decynylbenzolactam-V8
  参考文献：
  名称：

  General and Stereospecific Route to 9-Substituted, 8,9-Disubstituted, and 9,10-Disubstituted Analogues of Benzolactam-V8

  摘要：

  Nitration of the L-tyrosine derivative 9 provides the S-nitro compound 13', which is converted into amide 15 by reduction and protection. Nitration of 15 either ortho or para to the acetamido group gives 16 and 17. After reduction of the nitro group, the anilines 21b and 29b are coupled with triflate 22a, and then cyclized to afford lactams 24 and 31, respectively. By means of a Pd-catalyzed coupling reaction, 8-acetamido-4-decynylbenzolactam-V8 (26) and 9-decyny-10-acctamidobenzolactam-V8 (33) are obtained. The regioisomers 16 and 17 are transformed into a single isomer, 34, which is converted into 9-decynylbenzolactam-V8 (4). The K-i values for 4, 26, and 33 to displace PDBU binding from recombinant PKC alpha (PKC = protein kinase C) art! about 6, 173, and 16 nM. These results demonstrate that while the introduction of a substituent at; either the 8- or 10-position of the 9-substituted benzolactam-V8s lowers their binding affinity, these newly generated analogues still retain reasonably good potency for PKC.

  DOI：

  10.1021/jo990605h
• 作为产物：
  描述：

  L-酪氨酸 在 palladium on activated charcoal 2,6-二甲基吡啶 、 盐酸 、 氢氧化钾 、 sodium hydroxide 、 sodium nitrate 、 sodium tetrahydroborate 、 锂硼氢 、 氯化亚砜 、 copper diacetate 、 lanthanum nitrate 、 二苯基磷酸 、 氢气 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， -10.0~70.0 ℃ 、3.04 MPa 条件下， 反应 145.5h， 生成 (2S,5S)-9-Benzyloxy-5-hydroxymethyl-2-isopropyl-1,4,5,6-tetrahydro-2H-benzo[e][1,4]diazocin-3-one
  参考文献：
  名称：

  General and Stereospecific Route to 9-Substituted, 8,9-Disubstituted, and 9,10-Disubstituted Analogues of Benzolactam-V8

  摘要：

  Nitration of the L-tyrosine derivative 9 provides the S-nitro compound 13', which is converted into amide 15 by reduction and protection. Nitration of 15 either ortho or para to the acetamido group gives 16 and 17. After reduction of the nitro group, the anilines 21b and 29b are coupled with triflate 22a, and then cyclized to afford lactams 24 and 31, respectively. By means of a Pd-catalyzed coupling reaction, 8-acetamido-4-decynylbenzolactam-V8 (26) and 9-decyny-10-acctamidobenzolactam-V8 (33) are obtained. The regioisomers 16 and 17 are transformed into a single isomer, 34, which is converted into 9-decynylbenzolactam-V8 (4). The K-i values for 4, 26, and 33 to displace PDBU binding from recombinant PKC alpha (PKC = protein kinase C) art! about 6, 173, and 16 nM. These results demonstrate that while the introduction of a substituent at; either the 8- or 10-position of the 9-substituted benzolactam-V8s lowers their binding affinity, these newly generated analogues still retain reasonably good potency for PKC.

  DOI：

  10.1021/jo990605h

文献信息

• Phosphorylation-Inducing Chimeric Small Molecules
  作者：Sachini U. Siriwardena、Dhanushka N. P. Munkanatta Godage、Veronika M. Shoba、Sophia Lai、Mengchao Shi、Peng Wu、Santosh K. Chaudhary、Stuart L. Schreiber、Amit Choudhary

  DOI：10.1021/jacs.0c05537

  日期：2020.8.19

  Small molecules have been classically developed to inhibit enzyme activity; however, new classes of small molecules that endow new functions to enzymes via proximity-mediated effect are emerging. Phosphorylation (native or neo) of any given protein-of-interest can alter its structure and function, and we hypothesized that such modifications can be accomplished by small molecules that bring a kinase

  小分子已被经典开发用于抑制酶活性；然而，通过邻近介导效应赋予酶新功能的新型小分子正在出现。任何给定的目标蛋白质的磷酸化（天然或新）都可以改变其结构和功能，我们假设这种修饰可以通过使激酶接近目标蛋白质的小分子来完成。在此，我们描述了磷酸化诱导嵌合小分子 (PHICS)，它使两个示例激酶 - AMPK 和 PKC - 能够磷酸化不是这些激酶的底物的靶蛋白。PHICS 是通过将激酶和靶蛋白的小分子结合物连接起来形成的，并表现出双功能分子的几个特征，包括钩状效应、周转、同工型特异性、磷酸化的剂量和时间控制，以及依赖于接近度（即接头长度）的活性。使用 PHICS，我们能够通过 AMPK 或 PKC 诱导 BRD4 的天然和新磷酸化。此外，PHICS 诱导细胞中靶蛋白布鲁顿酪氨酸激酶的信号相关磷酸化。我们设想 PHICS 介导的天然或新磷酸化将在基础研究和医学中发挥作用。
• Stereospecific synthesis of 9-substituted benzolactam-V8 from L-tyrosine via regioselective aromatic nitration
  作者：Dawei Ma、Wenjun Tang

  DOI：10.1016/s0040-4039(98)01598-6

  日期：1998.10

  A new protocol for the synthesis of 9-substituted benzolactam-V8, a class of potent protein kinase C activators, from L-tyrosine through regioselective aromatic nitration, is described (C) 1998 Elsevier Science Ltd. All rights reserved.