tert-butyl 5S-5-amino-6-(methoxy(methyl)amino)-6-oxohexylcarbamate

• 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-butyl 5S-5-amino-6-(methoxy(methyl)amino)-6-oxohexylcarbamate
• 英文别名: H-Lys(Boc)-N(Me)OMe；[5-amino-5-(N-methoxy-N-methyl-carbamoyl)-pentyl]-carbamic acid tert-butyl ester
• 化学式: C₁₃H₂₇N₃O₄
• 分子量: 289.375
• InChiKey: BGIVJEONIPOJRJ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  20.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  93.89
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 5S-5-amino-6-(methoxy(methyl)amino)-6-oxohexylcarbamate 在 咪唑 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 羟胺 、 三正丁基氢锡 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 [5-amino-6-{5-[4-(3,4-dichlorophenethyloxy)phenylmethyl]-[1,2,4]oxadiazol-3-yl}-6-(tert-butyl-dimethylsilyloxy)-hexyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors

  摘要：

  Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P-2 binding pocket of human mast cell tryptase, while building in a high degree of selectivity over human trypsin and other serine proteases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.013
• 作为产物：
  描述：

  Nε-Boc-Nα-Cbz-L-赖氨酸 在 palladium on activated charcoal 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 tert-butyl 5S-5-amino-6-(methoxy(methyl)amino)-6-oxohexylcarbamate
  参考文献：
  名称：

  Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors

  摘要：

  Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P-2 binding pocket of human mast cell tryptase, while building in a high degree of selectivity over human trypsin and other serine proteases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.013

文献信息

• Mild, Rapid, and Chemoselective Procedure for the Introduction of the 9-Phenyl-9-fluorenyl Protecting Group into Amines, Acids, Alcohols, Sulfonamides, Amides, and Thiols
  作者：Jacob Soley、Scott D. Taylor

  DOI：10.1021/acs.joc.9b02809

  日期：2020.2.21

  well as into alcohols and carboxylic acids, rapidly and in excellent yields, using 9-chloro-9-phenylfluorene (PhFCl)/N-methylmorpholine (NMM)/AgNO3. Nα-PhF-protected amino acids can be prepared from unprotected α-amino acids, rapidly and often in near quantitative yields, by treatment with N,O-bis(trimethylsilyl)acetamide (BSA) and then PhFCl/NMM/AgNO3. Primary alcohols can be protected with the PhF group

  9-苯基-9-芴基（PhF）基团已被用作氨基酸及其衍生物的Nα保护基团，这主要是由于其具有防止外消旋作用的能力。但是，使用标准协议安装该组，该协议使用9-溴-9-苯基芴/ K3PO4 / Pb（NO3）2，通常需要几天的时间，并且产量可能会有所不同。在这里，我们证明了使用9-氯-9-苯基芴基（PhFCl ）/ N-甲基吗啉（NMM）/ AgNO3。可以先用N，O-双（三甲基甲硅烷基）乙酰胺（BSA）然后用PhFCl / NMM / AgNO3处理，由未保护的α-氨基酸快速且经常以接近定量的收率制备Nα-PhF保护的氨基酸。在仲醇存在下，可以用PhF基团保护伯醇，且产率适中。使用PhFCl / AgNO3，可以在伯铵盐或羧酸的存在下以高收率保护伯醇。使用苯芴基醇（PhFOH）/ BF3·OEt2 / K3PO4可以以中等至良好的收率保护伯磺酰胺和酰胺，而使用PhFOH / BF3·OEt2则
• Preparation, anti-trypanosomal activity and localisation of a series of dipeptide-based vinyl sulfones
  作者：William Doherty、Jinju James、Paul Evans、Laura Martin、Nikoletta Adler、Derek Nolan、Andrew Knox

  DOI：10.1039/c4ob01412j

  日期：——

  An improved, Weinreb amide-based, synthesis of anti-trypanosomal lysine-containing vinyl sulfones is described incorporating, as a feature, diversity at the ε-lysine amino group. Members of this family demonstrated moderate to good efficacy as anti-trypanosomal agents and a fluorescent dansyl (19) derivative was used to investigate subcellular localisation of the compound class.

  描述了一种改进的基于Weinreb酰胺的抗锥虫含赖氨酸的乙烯基砜的合成，其特征是在ε-赖氨酸氨基上具有多样性。该家族成员作为抗锥虫剂显示出中等至良好的功效，并且使用荧光丹磺酰（19）衍生物研究化合物类别的亚细胞定位。
• Synthesis and Evaluation of 1,2,3-Triazole-Containing Vinyl and Allyl Sulfones as Anti-Trypanosomal Agents
  作者：William Doherty、Nikoletta Adler、Andrew Knox、Derek Nolan、Joanna McGouran、Anna Pratima Nikalje、Deepak Lokwani、Aniket Sarkate、Paul Evans

  DOI：10.1002/ejoc.201601221

  日期：2017.1.3

  peptidyl vinyl sulfones as Trypanosoma brucei brucei inhibitors by using click chemistry, starting from a common azide intermediate. Among the triazole analogues, biotinylated inhibitors 11 and 12 offer possibilities as probes for the elucidation of target proteases for this compound class. The development of two syntheses of a 1,2,3-triazole-based vinyl sulfone 5 are also presented. This compound was accessed

  描述了一种通过使用点击化学从常见的叠氮化物中间体开始获得 1,2,3-三唑衍生的肽基乙烯基砜作为布氏锥虫抑制剂的方法。在三唑类似物中，生物素化抑制剂 11 和 12 提供了作为阐明此类化合物目标蛋白酶的探针的可能性。还介绍了 1,2,3-三唑基乙烯基砜 5 的两种合成方法。该化合物是通过赖氨酸衍生的叠氮化物（本身通过重氮转移获得）和苯丙氨酸衍生的炔烃的点击反应获得的，该炔烃通过基于 Ohira-Bestmann 和 Corey-Fuchs 的炔基化方案合成。该化合物家族的几个成员显示出有希望的抗锥虫活性。出乎意料的是，最活跃的化合物之一是烯丙基砜 24，它源于乙烯基砜 5 的异构化，可能是一种可逆抑制剂。对寄生半胱氨酸蛋白酶罗得沙因的活性位点中的类似物进行了对接研究，以便深入了解它们与这些酶的可能相互作用。
• WO2006/44133
  申请人：——

  公开号：——

  公开（公告）日：——
• Incorporation of Non-natural Amino Acids Improves Cell Permeability and Potency of Specific Inhibitors of Proteasome Trypsin-like Sites
  作者：Paul P. Geurink、Wouter A. van der Linden、Anne C. Mirabella、Nerea Gallastegui、Gerjan de Bruin、Annet E. M. Blom、Mathias J. Voges、Elliot D. Mock、Bogdan I. Florea、Gijs A. van der Marel、Christoph Driessen、Mario van der Stelt、Michael Groll、Herman S. Overkleeft、Alexei F. Kisselev

  DOI：10.1021/jm3016987

  日期：2013.2.14

  Proteasomes degrade the majority of proteins in mammalian cells by a concerted action of three distinct pairs of active sites. The chymotrypsin-like sites are targets of antimyeloma agents bortezomib and carfilzomib. Inhibitors of the trypsin-like site sensitize multiple myeloma cells to these agents. Here we describe systematic effort to develop inhibitors with improved potency and cell permeability, yielding azido-Phe-Leu-Leu-4-aminomethyl-Phe-methyl vinyl sulfone (4a, LU-102), and a fluorescent activity-based probe for this site. X-ray structures of 4a and related inhibitors complexed with yeast proteasomes revealed the structural basis for specificity. Nontoxic to myeloma cells when used as a single agent, 4a sensitized them to bortezomib and carfilzomib. This sensitizing effect was much stronger than the synergistic effects of histone acetylase inhibitors or additive effects of doxorubicin and dexamethasone, raising the possibility that cornbinations of inhibitors of the trypsin-like site with bortezomib or carfilzomib would have stronger antincoplastic activity than combinations currently used clinically.