(2S)-[(2S)-aminopropionylamino]-5-{[(3S)-((1S)-methylpropyl)-4-oxooxetane-(2R)-carbonyl]amino}pentanoic acid

• 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)-[(2S)-aminopropionylamino]-5-{[(3S)-((1S)-methylpropyl)-4-oxooxetane-(2R)-carbonyl]amino}pentanoic acid
• 英文别名: belactosin C；(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]pentanoic acid
• 化学式: C₁₆H₂₇N₃O₆
• 分子量: 357.407
• InChiKey: ZFCGPWGFGUDLHO-UHFZAUJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  L-异亮氨酸 在 palladium on activated charcoal 2,2,6,6-四甲基哌啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 tin(II) trifluoromethanesulfonate 、 正丁基锂 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 胸苷酸 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N'-二环己基碳二亚胺 、 hydroxylamine-O-sulfonic acid 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~100.0 ℃ 、101.33 kPa 条件下， 反应 132.0h， 生成 (2S)-[(2S)-aminopropionylamino]-5-{[(3S)-((1S)-methylpropyl)-4-oxooxetane-(2R)-carbonyl]amino}pentanoic acid
  参考文献：
  名称：

  Enantioselective Total Syntheses of Belactosin A, Belactosin C, and Its Homoanalogue

  摘要：

  Enantioselective total syntheses of belactosin A, belactosin C, and its homoanalogue have been accomplished in high overall yields (32% for belactosin A from the amino acid 10, and 35 and 36% for belactosin C and its homoanalogue, respectively). This concise approach comprises a novel sequential acylation/beta-lactonization reaction and allows a facile alteration of the substituents, thus providing a flexible route to a new family of highly active belactosin-based proteasome inhibitors.

  DOI：

  10.1021/ol049409+

文献信息

• Oppolzer Sultam Directed Aldol as a Key Step for the Stereoselective Syntheses of Antitumor Antibiotic Belactosin C and Its Synthetic Congeners^,
  作者：Gullapalli Kumaraswamy、Mogilisetti Padmaja、Bekkam Markondaiah、Nivedita Jena、Balasubramanian Sridhar、Marelli Udaya Kiran

  DOI：10.1021/jo0516887

  日期：2006.1.1

  An efficient protocol has been developed using d-(2R)-Oppolzer sultam as a chiral auxiliary for generating anti/syn diastereomers with high enantiopurity and utilized in the efficient synthesis of natural product belactosin C and their synthetic congeners. It has been observed that a variation in the stoichiometry of the Lewis acid led to a difference in anti/syn selectivity.

  已经开发出一种有效的方案，使用d-（2 R）-Oppolzer sultam作为手性助剂，以产生具有高对映体纯度的抗/ syn非对映异构体，并被用于天然产物Belactosin C及其合成同源物的高效合成。已经观察到路易斯酸的化学计量的变化导致抗/同步选择性的差异。
• Novel method for the asymmetric synthesis of beta-lactone compounds
  申请人：Smith W. Jeffrey

  公开号：US20060258620A1

  公开（公告）日：2006-11-16

  The present invention features methods of treating a cancer in a subject by administering an effective amount of a beta-lactone to the subject. The invention also features methods of inhibiting angiogenesis in a subject by administering an effective amount of an inhibitor of fatty acid synthase to the subject. These methods can be used to treat a variety of cancers and other diseases and conditions. The invention also features methods of identifying beta-lactones and other compounds that can be used in the methods of the invention for the treatment of tumors, inhibition of angiogenesis, and the treatment of diseases and conditions that involve pathological angiogenesis. The invention also features methods of synthesizing beta-lactones and features novel beta-lactone compounds.

  本发明涉及通过向患者施用有效量的β-内酰胺来治疗患者身上的癌症的方法。本发明还涉及通过向患者施用脂肪酸合成酶抑制剂的有效量来抑制患者身上的血管生成的方法。这些方法可以用于治疗各种癌症和其他疾病和病况。本发明还涉及识别β-内酰胺和其他化合物的方法，这些化合物可以用于本发明中用于治疗肿瘤、抑制血管生成以及治疗涉及病理性血管生成的疾病和病况的方法。本发明还涉及合成β-内酰胺的方法和新型β-内酰胺化合物的特点。
• Inhibition of fatty acid synthase by beta-lactones and other compounds for inhibition of cellular proliferation
  申请人：——

  公开号：US20040024050A1

  公开（公告）日：2004-02-05

  The present invention features methods of treating a cancer in a subject by administering an effective amount of a beta-lactone to the subject. The invention also features methods of inhibiting angiogenesis in a subject by administering an effective amount of an inhibitor of fatty acid synthase to the subject. These methods can be used to treat a variety of cancers and other diseases and conditions. The invention also features methods of identifying beta-lactones and other compounds that can be used in the methods of the invention for the treatment of tumors, inhibition of angiogenesis, and the treatment of diseases and conditions that involve pathological angiogenesis.
• NOVEL BELACTOSIN DERIVATIVES AS THERAPEUTIC AGENTS/BIOLOGICAL PROBES AND THEIR SYNTHESIS
  申请人：Romo Daniel

  公开号：US20090042922A1

  公开（公告）日：2009-02-12

  Derivatives of belactosin and their synthesis are disclosed. In certain embodiments, compounds of the present invention exhibit anti-cancer, antiviral, antibiotic, and/or auto-immune therapeutic abilities. In general, methods of synthesis disclosed herein allow for introduction of a variety of substituents at numerous positions as well as the facile introduction of a beta-lactone ring moiety. The synthetic steps comprise, in preferred embodiments, a tandem Mukaiyama aldol lactonization reaction. Data demonstrating the utility of some of the derivatives as proteasome inhibitors is also disclosed.
• US7728153B2
  申请人：——

  公开号：US7728153B2

  公开（公告）日：2010-06-01