ent-tubuphenylalanine hydrochloride | 1259283-28-7

• 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: ent-tubuphenylalanine hydrochloride
• CAS: 1259283-28-7
• 化学式: C₁₂H₁₇NO₂*ClH
• 分子量: 243.733
• InChiKey: UQYQCBIKWHIMKS-XQKZEKTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  16.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  63.32
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  ent-tubuphenylalanine hydrochloride 在 吡啶 、 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 水 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 79.0h， 生成 (2R,4S)-4-(2-((1S,3R)-1-acetoxy-4-methyl-3-((2S,3S)-3-methyl-2-((R)-1-methylpiperidine-2-carboxamido)pentanamido) pentyl)thiazole-4-carboxamido)-2-methyl-5-phenylpentanoicacid
  参考文献：
  名称：

  Synthesis and cytotoxicity evaluation of diastereoisomers and N-terminal analogues of tubulysin-U

  摘要：

  Tubulysins are potent anti-mitotic natural compounds and a scalable and efficient synthetic route for generation of its analogues has been developed and extended to the synthesis of diastereoisomers and N-terminal analogues of tubulysin-U. Structure-activity-relationship studies on these synthetic analogues reaffirmed the significance of native stereochemistry of tubulysins for optimal biological activity and cytotoxicity. However, while modification of Tup stereochemistry has only minor effect on the tubulysins cytotoxicity, Tuv stereochemistry is critically important and modification of either Tuv stereo-centre produced a dramatic drop in cytotoxicity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.09.010
• 作为产物：
  描述：

  (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,4S)-4-((tert-butoxycarbonyl)amino)-2-methyl-5-phenylpentanoate 在 盐酸 作用下， 以 水 为溶剂， 生成 ent-tubuphenylalanine hydrochloride
  参考文献：
  名称：

  Synthesis and cytotoxicity evaluation of diastereoisomers and N-terminal analogues of tubulysin-U

  摘要：

  Tubulysins are potent anti-mitotic natural compounds and a scalable and efficient synthetic route for generation of its analogues has been developed and extended to the synthesis of diastereoisomers and N-terminal analogues of tubulysin-U. Structure-activity-relationship studies on these synthetic analogues reaffirmed the significance of native stereochemistry of tubulysins for optimal biological activity and cytotoxicity. However, while modification of Tup stereochemistry has only minor effect on the tubulysins cytotoxicity, Tuv stereochemistry is critically important and modification of either Tuv stereo-centre produced a dramatic drop in cytotoxicity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.09.010

文献信息

• Total Syntheses of Tubulysins
  作者：Taku Shibue、Toshihiro Hirai、Iwao Okamoto、Nobuyoshi Morita、Hyuma Masu、Isao Azumaya、Osamu Tamura

  DOI：10.1002/chem.201000963

  日期：——

  (S)‐4‐isopropyl‐3‐propionyl‐2‐oxazolidinone with N‐protected phenylalaninal and a subsequent Barton deoxygenation protocol. We accomplished the total syntheses of tubulysins U (1 c) and V (1 d) by using these methodologies, in which the isoxazolidine ring was used as the effective protective group for γ‐amido alcohol functionality. Furthermore, to understand the structure‐activity relationship of tubulysins

  描述了作为强效微管蛋白聚合抑制剂的四肽微管蛋白溶素D（1b），U（1 c）和V（1 d）的总合成。Tuv（2）的合成是微管蛋白的一种不常见的氨基酸组成，包括衍生自D-古洛糖的手性硝酮D - 6与N-丙烯酰基樟脑（s）9的1,3-偶极环加成反应，采用双不对称诱导，而另一种不常见的氨基酸Tup（20）的合成涉及由（S）生成的（Z）-硼烯醇盐的立体选择性Evans aldol反应）带有N保护的苯丙氨酸的4-异丙基-3-丙酰基-2-恶唑烷酮和随后的Barton脱氧方案。通过使用这些方法，我们完成了微管溶素U（1 c）和V（1 d）的总合成，其中异恶唑烷环用作γ-氨基醇官能团的有效保护基。此外，为了了解微管溶素的结构-活性关系，我们合成了微管蛋白抑制剂d（图1b）和环-微管蛋白抑制剂d（图1e）由2 -Me和20，和ENT -tubulysin d（ENT - 1 d）从ENT - 2个‐Me和eNT