paracaseolide A

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: paracaseolide A
• 英文别名: (+/-)-paracaseolide A；(1R,6R,7S,10S,11R,12S)-6-dodecyl-1,10-dimethyl-7-[(E)-tetradec-1-enyl]-2,9,13-trioxatetracyclo[8.2.1.04,12.07,11]tridec-4-ene-3,8-dione
• 化学式: C₃₈H₆₂O₅
• 分子量: 598.907
• InChiKey: ZAFZFHLQBNISDI-VUOKYHFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.7
• 重原子数：
  43
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  paracaseolide A 在 臭氧 、 二甲基硫 作用下， 以 二氯甲烷 为溶剂， 以97.2%的产率得到(1S,4S,5R,10R,11S,12R)-5-dodecyl-1,10-dimethyl-3,8-dioxo-2,9,13-trioxatetracyclo[8.2.1.0�?�,.0�?�,]tridec-6-ene-4-carbaldehyde (14)
  参考文献：
  名称：

  Design and synthesis of paracaseolide A analogues as selective protein tyrosine phosphatase 1B inhibitors

  摘要：

  研究人员合成了一系列结构相关的天然产物 Paracaseolide A 类似物，并将其鉴定为强效 PTP1B 抑制剂。在这些类似物中，化合物 10 尤其显示出更强的 PTP1B 酶抑制活性、对 PTP1B 而非 TC-PTP 的高选择性以及更好的细胞效应。

  DOI：

  10.1039/c4ob00214h
• 作为产物：
  描述：

  2,5-二甲基呋喃 在 溴化亚铜二甲硫醚 、 magnesium monoperoxyphthalate hexahydrate 、 sodium hydride 、 臭氧 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 间氯过氧苯甲酸 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.83h， 生成 paracaseolide A
  参考文献：
  名称：

  Total Synthesis of Paracaseolide A

  摘要：

  The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification.

  DOI：

  10.1021/ol303447r

文献信息

• Total synthesis of novel bioactive natural product paracaseolide A and analogues: computational evaluation of a ‘proposed’ biomimetic Diels–Alder reaction
  作者：Laxmaiah Vasamsetty、Debashis Sahu、Bishwajit Ganguly、Faiz Ahmed Khan、Goverdhan Mehta

  DOI：10.1016/j.tet.2014.09.072

  日期：2014.11

  A short and generally applicable synthesis of bioactive tetracyclic natural product paracaseolide A has been accomplished employing a ‘proposed’ biomimetic Diels–Alder reaction as the key strategic step. The Diels–Alder precursors for this purpose were readily assembled through a versatile Suzuki coupling on preformed α-halo butenolides. The mechanistic aspects of the ‘putative’ biomimetic Diels–Alder

  使用拟议的仿生狄尔斯-阿尔德反应作为关键的战略性步骤，已完成了对生物活性四环天然产物对酪蛋白内酯A的短暂合成且普遍适用。为此，Diels–Alder前体可通过通用的Suzuki偶联剂容易地组装在预先形成的α-卤代丁烯内酯上。已使用计算方法探究了“公认的”仿生Diels-Alder反应的机理，这表明这种[4 + 2]-环加成反应是通过逐步过程进行的，并且产物的分布是受热力学控制的。
• Total synthesis of a novel oxa-bowl natural product paracaseolide A via a ‘putative’ biomimetic pathway
  作者：Laxmaiah Vasamsetty、Faiz Ahmed Khan、Goverdhan Mehta

  DOI：10.1016/j.tetlet.2013.04.097

  日期：2013.7

  A total synthesis of bioactive tetracyclic natural product paracaseolide A, embodying an architecturally unusual oxa-bowl framework, has been accomplished from commercially available 5-methyl-2-furfural. The key step involving a thermal [4+2]-dimerization of an appropriately crafted 5-methyl-3-alkenylbutenolide is shown to proceed in a stepwise manner. (c) 2013 Elsevier Ltd. All rights reserved.
• Streamlined biomimetic synthesis of paracaseolide A via aerobic oxidation of a 2-silyloxyfuran
  作者：John Boukouvalas、Marc-Alexandre Jean

  DOI：10.1016/j.tetlet.2014.05.054

  日期：2014.7

  A simple, bioinspired synthesis of the naturally occurring Cdc25B inhibitor paracaseolide A is reported. Key steps include: (i) an aerobic oxidation of a 2-silyloxyfuran to the corresponding silyl ketoester, and (ii) the preparation of the former intermediate by silylation of an alpha-alkylidenebutenolide. Both of these high-yielding transformations are unprecedented. (C) 2014 Elsevier Ltd. All rights reserved.
• Total Synthesis of Paracaseolide A
  作者：Tezcan Guney、George A. Kraus

  DOI：10.1021/ol303447r

  日期：2013.2.1

  The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification.
• Design and synthesis of paracaseolide A analogues as selective protein tyrosine phosphatase 1B inhibitors
  作者：Jian-Peng Yin、Chun-Lan Tang、Li-Xin Gao、Wei-Ping Ma、Jing-Ya Li、Ying Li、Jia Li、Fa-Jun Nan

  DOI：10.1039/c4ob00214h

  日期：——

  A series of structurally related analogues of the natural product paracaseolide A were synthesized and identified as potent PTP1B inhibitors. Among these analogues, compound 10 in particular showed improved PTP1B enzyme inhibitory activity, high selectivity for PTP1B over TC-PTP, and improved cellular effects.

  研究人员合成了一系列结构相关的天然产物 Paracaseolide A 类似物，并将其鉴定为强效 PTP1B 抑制剂。在这些类似物中，化合物 10 尤其显示出更强的 PTP1B 酶抑制活性、对 PTP1B 而非 TC-PTP 的高选择性以及更好的细胞效应。