(4R)-4-(tert-butoxycarbonylamino)-5-methyl-3-oxo-hexanoic acid methyl ester | 663918-97-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: (4R)-4-(tert-butoxycarbonylamino)-5-methyl-3-oxo-hexanoic acid methyl ester
• 英文别名: (4R)-4-(tert-butoxycarbonylamino)-5-methyl-3-oxohexanoic acid methyl ester；4R-tert-butoxycarbonylamino-5-methyl-3-oxohexanoic acid methyl ester；(R)-methyl 4-((tert-butoxycarbonyl)amino)-5-methyl-3-oxohexanoate；(4R)-4-tert-Butoxycarbonylamino-5-methyl-3-oxohexanoic Acid Methyl Ester；methyl (4R)-5-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxohexanoate
• CAS: 663918-97-6
• 化学式: C₁₃H₂₃NO₅
• 分子量: 273.329
• InChiKey: DDNICKQGRHYVOS-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-4-(tert-butoxycarbonylamino)-5-methyl-3-oxo-hexanoic acid methyl ester 在 咪唑 、 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 钾硼氢 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 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 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.33h， 生成 benzyl (2S)-1-[(2S)-2-[[(2S)-2-[(3S,4R)-3-hydroxy-5-methyl-4-[[(2S,3R)-3-[(2S)-2-[methyl(phenylmethoxycarbonyl)amino]-3-naphthalen-2-ylpropanoyl]oxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]hexanoyl]oxy-3-methylbutanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  玉兰素B类似物的全合成及生物学评价

  摘要：

  丹丹素A和B是一类海洋天然环二肽，其结构和生物活性与二羟肌酐密切相关。合成的坦丹更容易获得，从而加快了该抗肿瘤，抗病毒和免疫抑制化合物家族新的大环衍生物的制备。通过将大内酰胺化位点从Nst 1和Thr 6更改为Pro 4和N，O -Me 2 Tyr 5来优化先前报道的合成坦丹林的合成路线残留物导致反应产率的显着提高。使用这种新的合成方法，制备了tamandarin B的四个新的大环类似物，并评估了其抗癌活性。这些结果提供了进一步的见解，其坦丹林和双精胺的结构活性关系。

  DOI：

  10.1021/jo070412r
• 作为产物：
  描述：

  D-缬氨酸 在 吡啶 、 碳酸氢钠 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.75h， 生成 (4R)-4-(tert-butoxycarbonylamino)-5-methyl-3-oxo-hexanoic acid methyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Tamandarin B Analogues

  摘要：

  [GRAPHICS]The synthesis of two tamandarin B analogues in which the N,O-Me(2)Tyr(5) unit was replaced by N-Me-phenylaianine (N-MePhe(5)) and (S)-2(methylamino)-3-(naphthalen-2-yl)propanoic acid (N-MeNaphth(5)) is described. The choice of the macrocyclization site was crucial to achieve satisfactory macrolactamization. Coupling between norstatine (Nst(1)) and threonine (Thr(6)) afforded only a 15% yield, while lactamization between proline (Pro(4)) and the aromatic moiety could be achieved in 65% yield.

  DOI：

  10.1021/ol0530023

文献信息

• Total Synthesis and Stereochemical Revision of Burkholdac A
  作者：Zhengshuang Xu、Tao Ye、Junyang Liu、Xiao Ma、Yuqing Liu、Zhuo Wang、Shuqin Kwong、Qi Ren、Shoubin Tang、Yi Meng

  DOI：10.1055/s-0031-1290339

  日期：2012.3

  A stereocontrolled total synthesis of burkholdac A was completed, leading to a revision of the reported stereochemistry. burkholdac A - total synthesis - antitumor - stereochemical assignment

  立体控制的Burkholdac A的总合成完成，从而导致了报道的立体化学的修订。 burkholdac A-全合成-抗肿瘤-立体化学分配
• Tamandarin analogs and fragments thereof and methods of making and using
  申请人：Joullie M. Madeleine

  公开号：US20070149446A1

  公开（公告）日：2007-06-28

  The present invention is directed to a compound of Formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , W, X, Y, and Z are defined herein. The compounds of the present invention are useful as anticancer agents. Specifically, the compounds are useful for treating or preventing cancer and tumor growth. The present invention is also directed to compositions comprising a compound according to the above formula. The present invention is also directed to methods of using a compound according to the above formula.

  本发明涉及公式I中R1、R2、R3、R4、R5、R6、W、X、Y和Z所定义的化合物。本发明的化合物可用作抗癌剂。具体而言，这些化合物可用于治疗或预防癌症和肿瘤生长。本发明还涉及包括上述公式中化合物的组合物。本发明还涉及使用上述公式中化合物的方法。
• Modulators of ROR-gamma
  申请人：Vitae Pharmaceuticals, LLC

  公开号：US11008340B2

  公开（公告）日：2021-05-18

  Provided are novel compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

  本发明提供了式 I 的新型化合物：其药学上可接受的盐及其药物组合物，它们可用于治疗由 RORγ 介导的疾病和失调。还提供了包含式 I 新型化合物的药物组合物及其用于治疗一种或多种炎症、代谢、自身免疫和其他疾病或紊乱的方法。
• Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase Inhibitor
  作者：Alexander Yurek-George、Fay Habens、Matthew Brimmell、Graham Packham、A. Ganesan

  DOI：10.1021/ja039258q

  日期：2004.2.1

  The total synthesis of spiruchostatin A was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction and as an activated acylating agent for amide formation, and macrolactonization by the Yamaguchi protocol. Spiruchostatin A is shown to have biological activity similar to that of FK228, a potent histone deacetylase (HDAC) inhibitor in clinical trials. The spiruchostatin A analogue, epimeric at the beta-hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.
• [EN] MODULATORS OF ROR-GAMMA<br/>[FR] MODULATEURS DE ROR-GAMMA
  申请人：VITAE PHARMACEUTICALS INC

  公开号：WO2017087608A8

  公开（公告）日：2017-07-06