[tert-butoxycarbonyl(pent-4-enoyl)amino] tert-butyl carbonate | 951326-69-5

• 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: [tert-butoxycarbonyl(pent-4-enoyl)amino] tert-butyl carbonate
• 英文别名: Tert-butyl [(2-methylpropan-2-yl)oxycarbonyl-pent-4-enoylamino] carbonate；tert-butyl [(2-methylpropan-2-yl)oxycarbonyl-pent-4-enoylamino] carbonate
• CAS: 951326-69-5
• 化学式: C₁₅H₂₅NO₆
• 分子量: 315.367
• InChiKey: WTZTUOYSWLYJJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [tert-butoxycarbonyl(pent-4-enoyl)amino] tert-butyl carbonate 在 Grubbs catalyst first generation 、 palladium 10% on activated carbon 、 氢气 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 10.0h， 生成 [tert-butoxycarbonyl-[8-[tert-butoxycarbonyl(tert-butoxycarbonyloxy)amino]-8-oxooctanoyl]amino]tert-butyl carbonate
  参考文献：
  名称：

  Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates

  摘要：

  Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.011
• 作为产物：
  描述：

  4-戊烯酰氯 、 N,O-二叔丁氧羰基-羟胺 在 吡啶 作用下， 反应 5.0h， 以79%的产率得到[tert-butoxycarbonyl(pent-4-enoyl)amino] tert-butyl carbonate
  参考文献：
  名称：

  Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates

  摘要：

  Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.11.011

文献信息

• Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling
  作者：Samuel Bouchet、Camille Linot、Dusan Ruzic、Danica Agbaba、Benoit Fouchaq、Joëlle Roche、Katarina Nikolic、Christophe Blanquart、Philippe Bertrand

  DOI：10.1021/acsmedchemlett.8b00440

  日期：2019.6.13

  of a new small series of human histone deacetylases (HDAC) inhibitors. Alkenes bearing Boc-protected hydroxamic acid and benzamide and trityl-protected thiols were used to provide the zinc binding groups and were reacted with alkenes bearing aromatic cap groups. One compound was identified as a selective HDAC6 inhibitor lead. Additional biological evaluation in cancer cell lines demonstrated its ability

  烯烃的不对称交叉复分解作为一种收敛的通用合成策略，允许制备新的小系列人组蛋白脱乙酰基酶（HDAC）抑制剂。带有Boc保护的异羟肟酸和苯甲酰胺和三苯甲基保护的硫醇的烯烃被用来提供锌结合基团，并与带有芳族封端基团的烯烃反应。一种化合物被鉴定为选择性HDAC6抑制剂。癌细胞系中的其他生物学评估表明，它具有刺激上皮标记物E-钙粘着蛋白和肿瘤抑制基因（如SEMA3F和p21）表达的能力，表明该化合物在肺癌治疗中的潜在用途。所有11种HDAC同工型上的分子对接用于使观察到的生物学结果合理化。
• Syntheses of Thailandepsin B Pseudo‐Natural Products: Access to New Highly Potent HDAC Inhibitors via Late‐Stage Modification
  作者：Jana Brosowsky、Monika Lutterbeck、Amelie Liebich、Manfred Keller、Daniel Herp、Anja Vogelmann、Manfred Jung、Bernhard Breit

  DOI：10.1002/chem.202002449

  日期：2020.12.9

  offers the possibility to introduce varying warheads via late stage modification. Additionally, it gives access to the asymmetric branched allylic ester moiety of the natural product in a highly diastereoselective manner applying rhodium‐catalyzed hydrooxycarbonylation. The newly developed pseudo‐natural products are extremely potent and selective HDAC inhibitors. The non‐proteinogenic amino acid d‐norleucine

  新的Thaiepsin B假天然产物已经制备。我们的综合策略提供了通过后期修改引入不同弹头的可能性。此外，它还可以通过铑催化的氢氧羰基化以非对映选择性的方式获得天然产物的不对称支链烯丙基酯部分。新开发的伪天然产物是非常有效和选择性的HDAC抑制剂。通过最近开发的铑催化加氢胺化方法，对映选择性地获得了非蛋白氨基酸的d-正亮氨酸。
• Design, synthesis and biological evaluation of 1,4-benzodiazepine-2,5-dione-based HDAC inhibitors
  作者：Lynda Loudni、Joëlle Roche、Vincent Potiron、Jonathan Clarhaut、Christian Bachmann、Jean-Pierre Gesson、Isabelle Tranoy-Opalinski

  DOI：10.1016/j.bmcl.2007.06.067

  日期：2007.9

  New histone deacetylase inhibitors have been synthesized and evaluated for their activity against non-small lung cancer cell line H661. These compounds have been designed with diversely substituted 1,4-benzodiazepine-2,5-dione moieties as cyclic peptide mimic cap structures, and a hydroxamate side chain. Biological evaluations demonstrated that benzodiazepine-based HDACi bearing an aromatic substituent at the N1 position exhibited promising anti proliferative and HDAC-inhibitory activities. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis of a selective HDAC6 inhibitor active in neuroblasts
  作者：Vincent Zwick、Claudia A. Simões-Pires、Alessandra Nurisso、Charlotte Petit、Carolina Dos Santos Passos、Giuseppe Marco Randazzo、Nadine Martinet、Philippe Bertrand、Muriel Cuendet

  DOI：10.1016/j.bmcl.2016.09.011

  日期：2016.10

  In recent years, the role of HDAC6 in neurodegeneration has been partially elucidated, which led some authors to propose HDAC6 inhibitors as a therapeutic strategy to treat neurodegenerative diseases. In an effort to develop a selective HDAC6 inhibitor which can cross the blood brain barrier (BBB), a modified hydroxamate derivative (compound 3) was designed and synthetized. This compound was predicted to have potential for BBB penetration based on in silico and in vitro evaluation of passive permeability. When tested for its HDAC inhibitory activity, the IC50 value of compound 3 towards HDAC6 was in the nM range in both enzymatic and cell-based assays. Compound 3 showed a cell-based selectivity profile close to that of tubastatin A in SH-SY5Y human neuroblastoma cells, and a good BBB permeability profile. (C) 2016 Elsevier Ltd. All rights reserved.
• Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates
  作者：Vincent Zwick、Alessandra Nurisso、Claudia Simões-Pires、Samuel Bouchet、Nadine Martinet、Attila Lehotzky、Judit Ovadi、Muriel Cuendet、Christophe Blanquart、Philippe Bertrand

  DOI：10.1016/j.bmcl.2015.11.011

  日期：2016.1

  Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect. (C) 2015 Elsevier Ltd. All rights reserved.