syringolin B | 235096-66-9

• 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: syringolin B
• 英文别名: (2S)-2-[[(2S)-1-[[(3E,5S,8S)-2,7-dioxo-5-propan-2-yl-1,6-diazacyclododec-3-en-8-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoylamino]-3-methylbutanoic acid
• CAS: 235096-66-9
• 化学式: C₂₄H₄₁N₅O₆
• 分子量: 495.619
• InChiKey: AIMDTYKFJMYVNG-NGGLIGEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  166
• 氢给体数：
  6
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-alpha-叔丁氧羰基-L-赖氨酸 在 aluminum (III) chloride 、 N-羟基丁二酰亚胺 、 甲基乙基硫醚 、 四甲基乙二胺 、 氢溴酸 、 zinc trifluoromethanesulfonate 、 sodium carbonate 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 37.25h， 生成 syringolin B
  参考文献：
  名称：

  Syntheses and cytotoxicity of syringolin B-based proteasome inhibitors

  摘要：

  The concise and modular total synthesis of the bacterial natural product and irreversible proteasome inhibitor syringolin B has been achieved. This synthesis has enabled the ready preparation of three diverse, structurally modified syringolin derivatives. The actions of these compounds in inhibiting the proliferation of neuroblastoma cell lines was evaluated, and significant enhancements in potency compared to the natural product were realized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.09.048

文献信息

• Total Synthesis of Syringolin A and B
  作者：Michael C. Pirrung、Goutam Biswas、Tannya R. Ibarra-Rivera

  DOI：10.1021/ol100761z

  日期：2010.5.21

  Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the α,β-unsaturated 12-membered lactam via intramolecular Horner−Wadsworth−Emmons reaction. Such reactions have been broadly used to prepared macrolactones, but this work presents a rarer example of its application to macrolactams. The final steps involved attachment

  据报道，两种最近发现的蛋白酶体抑制剂丁香脂素A和丁香酚B的总合成。我们方法的关键是通过分子内Horner-Wadsworth-Emmons反应生成α，β-不饱和12元内酰胺。这种反应已被广泛用于制备大内酯，但是这项工作为大内酰胺提供了一个罕见的例子。最终步骤包括使用肽偶联方法，包括基于未保护的缬氨酸N-羧酸酐的方法连接双（戊烯基）脲侧链。通过交叉复分解产生了丁香环素A的另外的烯烃。
• DEVELOPMENT OF A SYNTHESIS OF SYRINGOLIN A AND B AND DERIVATIVES THEREOF
  申请人：Kaiser Markus

  公开号：US20100022767A1

  公开（公告）日：2010-01-28

  The synthesis of syringolin A and B and derivatives thereof as well as to pharmaceutical compositions containing the syringolin A or B or derivatives thereof and the use of syringolin A and B and derivatives thereof for prophylaxis and treatment of cancer.

  合成Syringolin A和B及其衍生物，以及含有Syringolin A或B或其衍生物的药物组合物的用途，以及Syringolin A和B及其衍生物用于预防和治疗癌症。
• Derivatives of syringolin A
  申请人：Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V.

  公开号：EP2210881A1

  公开（公告）日：2010-07-28

  The present invention relates to syringolin A derivatives, the use of the syringolin A derivatives for prophylaxis and treatment of neurodegenerative diseases and proliferative diseases such as cancer, pharmaceutical compositions containing at least one syringolin A derivative as well as to a synthesis for preparing the syringolin A derivatives.

  本发明涉及丝菌素A衍生物，使用丝菌素A衍生物预防和治疗神经退行性疾病和增殖性疾病，如癌症，含有至少一种丝菌素A衍生物的药物组合物，以及制备丝菌素A衍生物的合成方法。
• Enzymatic Timing and Tailoring of Macrolactamization in Syringolin Biosynthesis
  作者：William M. Wuest、Daniel Krahn、Markus Kaiser、Christopher T. Walsh

  DOI：10.1021/ol2016687

  日期：2011.9.2

  The enzymatic activation of 3,4-dehydrolysine and subsequent formation of the 12-membered syringolin macrolactam were investigated. The timing of the desaturation was elucidated through the analysis of the initial adenylation domain of SylD. The SylD-TTE didomain was characterized and demonstrated to be the catalyst for formation of 12-membered macrocycles. When the SylD thioesterase domain was reacted with a family of acyclic CoA both natural and unnatural macrocycles were generated.
• SYNTHESIS OF SYRBACTIN PROTEASOME INHIBITORS
  申请人：Pirrung Michael C.

  公开号：US20130065872A1

  公开（公告）日：2013-03-14

  The disclosure relates generally to methods for the preparation of a family of natural compounds, the syrbactins and their analogs.