tert-butyl allyl-(3-hydroxy-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-enyl)carbamate | 1020733-33-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl allyl-(3-hydroxy-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-enyl)carbamate
• 英文别名: tert-butyl N-[(E,3S)-3-hydroxy-4-methyl-5-(2-methyl-1,3-thiazol-4-yl)pent-4-enyl]-N-prop-2-enylcarbamate
• CAS: 1020733-33-8
• 化学式: C₁₈H₂₈N₂O₃S
• 分子量: 352.498
• InChiKey: JGCUBQDPKWXWPA-BYIUCRAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl allyl-(3-hydroxy-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-enyl)carbamate 、 (3S,6R,7S,8S)-3,7-bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-4,4,6,8-tetramethyl-5-oxodec-9-enoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以77%的产率得到(3S,6R,7S,8S)-((S,E)-5-(tert-butoxycarbonyl)-2-methyl-1-(2-methylthiazol-4-yl)-pent-1-en-3-yl) 3,7-bis(tert-butyldimethylsilyloxy)-4,4,6,8-tetramethyl-5-oxodec-9-enoate
  参考文献：
  名称：

  Synthesis and Biological Activity of 12-Aza-Epothilones (Azathilones) – Non-Natural Natural Products with Potent Antiproliferative Activity

  摘要：

  12-Aza-epothilones（“Azathilones”）1和2通过环内烯烃交换或基于大环内酯化反应的环化反应制备。虽然分别使用双烯烃9和12的RCM非常有效，并产生高E选择性的大环烯烃，但随后的9,10-双键还原被证明出乎意料地困难和低产率。通过大环内酯化也成功制备了azathilone 2，这种方法被发现更有效。化合物2是体外人类癌细胞生长的高效抑制剂。这种类似物的活性与Epo A相当，无论是对于药物敏感的人类癌细胞的细胞毒性还是其微管聚合活性。然而，与Epo A相比，2对多药耐药癌细胞的作用显著较弱。

  DOI：

  10.2533/chimia.2007.143
• 作为产物：
  描述：

  tert-butyl allyl-(3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-enyl)carbamate 在 四丁基氟化铵 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以81%的产率得到tert-butyl allyl-(3-hydroxy-4-methyl-5-(2-methylthiazol-4-yl)-pent-4-enyl)carbamate
  参考文献：
  名称：

  Synthesis of 12-aza analogs of epothilones and (E)-9,10-dehydroepothilones

  摘要：

  N-Boc-12-aza-epothilone analog (azathilone) 1 is a potent inhibitor of human cancer cell growth and represents a structurally new class of natural product-derived microtubule-stabilizing agents. Compound 1 has been prepared employing a convergent strategy that is based on the consecutive assembly of building blocks 3, 4, and 19 into diene 20 and subsequent RCM-mediated macrocycle formation. The aldol reaction between aldehyde 3 and ketone 4 delivered the required 6R,7S diastereoisomer 5 with good selectivity and provided a reliable entry into the stereoselective synthesis of carboxylic acid 12. RCM with diene 20 was highly E-selective, thus giving efficient access to (E)-9,10-dehydro-1 (2). The latter is a key analog in SAR studies with 1. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.06.017

文献信息

• Synthesis and Biological Activity of 12-Aza-Epothilones (Azathilones) – Non-Natural Natural Products with Potent Antiproliferative Activity
  作者：Fabian Feyen、Jürg Gertsch、Markus Wartmann、Karl-Heinz Altmann

  DOI：10.2533/chimia.2007.143

  日期：——

  12-Aza-epothilones ('Azathilones') 1 and 2 have been prepared through ring-closing olefin metathesis or macrolactonization-based cyclization reactions. While RCM of the respective dienes 9 and 12 was found to be very effective and produced macrocyclic olefins with high E selectivity, the subsequent reduction of the 9,10-double bond proved to be unexpectedly difficult and low-yielding. Preparation of azathilone 2 was also accomplished via macrolactonization and this approach was found to be more effective. Compound 2 is a highly potent inhibitor of human cancer cell growth in vitro. The activity of this analog is comparable with that of Epo A, both in terms of cytotoxicity against drug-sensitive human cancer cells as well as its tubulin-polymerizing activity. However, in contrast to Epo A, 2 is considerably less potent against multidrug-resistant cancer cells.

  12-Aza-epothilones（“Azathilones”）1和2通过环内烯烃交换或基于大环内酯化反应的环化反应制备。虽然分别使用双烯烃9和12的RCM非常有效，并产生高E选择性的大环烯烃，但随后的9,10-双键还原被证明出乎意料地困难和低产率。通过大环内酯化也成功制备了azathilone 2，这种方法被发现更有效。化合物2是体外人类癌细胞生长的高效抑制剂。这种类似物的活性与Epo A相当，无论是对于药物敏感的人类癌细胞的细胞毒性还是其微管聚合活性。然而，与Epo A相比，2对多药耐药癌细胞的作用显著较弱。
• Synthesis of 12-aza analogs of epothilones and (E)-9,10-dehydroepothilones
  作者：Fabian Feyen、Andrea Jantsch、Kurt Hauenstein、Bernhard Pfeiffer、Karl-Heinz Altmann

  DOI：10.1016/j.tet.2008.06.017

  日期：2008.8

  N-Boc-12-aza-epothilone analog (azathilone) 1 is a potent inhibitor of human cancer cell growth and represents a structurally new class of natural product-derived microtubule-stabilizing agents. Compound 1 has been prepared employing a convergent strategy that is based on the consecutive assembly of building blocks 3, 4, and 19 into diene 20 and subsequent RCM-mediated macrocycle formation. The aldol reaction between aldehyde 3 and ketone 4 delivered the required 6R,7S diastereoisomer 5 with good selectivity and provided a reliable entry into the stereoselective synthesis of carboxylic acid 12. RCM with diene 20 was highly E-selective, thus giving efficient access to (E)-9,10-dehydro-1 (2). The latter is a key analog in SAR studies with 1. (C) 2008 Elsevier Ltd. All rights reserved.