(-)-amphidinolide P

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (-)-amphidinolide P
• 英文别名: amphidinolide P；(1R,2S,4R,7E,9R,13R,14S)-13-hydroxy-14-methyl-9-[(2S)-3-methylbut-3-en-2-yl]-6,15-dimethylidene-3,10,17-trioxatricyclo[11.3.1.02,4]heptadec-7-en-11-one
• 化学式: C₂₂H₃₀O₅
• 分子量: 374.477
• InChiKey: OHHBGABQODNLQQ-NUSBVJEGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  惕格酸 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 正丁基锂 、 Hoveyda-Grubbs catalyst second generation 、 三正丁胺 、 六氯丙酮 、 三氯硅烷 、 silver trifluoromethanesulfonate 、 碳酸氢钠 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 二异丙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， -78.0~110.0 ℃ 、413.7 kPa 条件下， 反应 119.5h， 生成 (-)-amphidinolide P
  参考文献：
  名称：

  Two Ene–Yne Metathesis Approaches to the Total Synthesis of Amphidinolide P

  摘要：

  The total synthesis of amphidinolide P was achieved through two different ene-yne metathesis, approaches. In each approach, the metathesis step was performed at late stages in the synthesis with all other functionality present. By forging two successful pathways to the synthesis of 1, some of the strengths and weaknesses of metathesis-intensive synthetic strategies were identified.

  DOI：

  10.1021/acs.orglett.5b01601

文献信息

• Ru-Catalyzed Alkene−Alkyne Coupling. Total Synthesis of Amphidinolide P
  作者：Barry M. Trost、Julien P. N. Papillon、Thomas Nussbaumer

  DOI：10.1021/ja055967n

  日期：2005.12.1

  unsaturated ruthenium complex catalyzed the formation of a carbon-carbon bond between two judiciously chosen alkene and alkyne partners in good yield, and in a chemo- and regioselective fashion, despite the significant degree of unsaturation of the substrates. The resulting 1,4-diene forms the backbone of the cytotoxic marine natural product amphidinolide P. The alkene partner was rapidly assembled from (R)-glycidyl

  尽管底物具有显着的不饱和度，但配位不饱和钌络合物以良好的产率、化学和区域选择性的方式催化了两个精心选择的烯烃和炔烃伙伴之间碳-碳键的形成。由此产生的 1,4-二烯形成了细胞毒性海洋天然产物两栖内酯 P 的骨架。烯烃伴侣由 (R)-甲苯磺酸缩水甘油酯快速组装而成，它是单瓶连续三组分偶联过程的关键使用乙烯基锂和乙烯基氰铜酸酯。炔烃配偶体的合成利用了在螯合控制条件下由顺式乙酸衍生的烯丙基锡试剂的不寻常的反选择性加成。此外，还具有使用偶氮二羧酸酯-三苯基膦系统的显着E选择性E2工艺。还介绍了使用 β-内酯作为热力学弹簧来实现大内酯化的第一个例子。因此，氧杂环丁酮环被用作有效的保护基团，提高了该全合成的整体效率。这项工作也是进一步探讨钌催化的烯烃-炔烃偶联范围的机会，特别是使用烯炔，并描述了使用各种官能化底物的研究。
• Convergent and Enantioselective Total Synthesis of (−)-Amphidinolide O and (−)-Amphidinolide P
  作者：Min-ho Hwang、Seo-Jung Han、Duck-Hyung Lee

  DOI：10.1021/ol401357k

  日期：2013.7.5

  A convergent and enantioselective total synthesis of (−)-amphidinolide O (1) and P (2), 15-membered macrolides with seven chiral centers along with many functional groups, is described. The key reactions include enantioselective Brown allylation, anti- and syn-selective aldol reactions, (E)-selective olefin metathesis, conformation-controlled stereoselective epoxidation, and selective introduction

  描述了一种具有七个手性中心以及许多官能团的15-元大环内酯（-）-两性内酯O（1）和P（2）的会聚和对映选择性全合成。关键反应包括对映体选择性布朗烯丙基化，抗-和顺式-选择性羟醛缩合反应，（ë） -选择性烯烃复分解，构象控制的立体选择性环氧化，并且选择性地引入环外亚甲基基团。还详细讨论了天然（+）-两性内酯O（ent - 1）和P（ent - 2）的绝对立体化学的分配。
• Alkene−Alkyne Coupling as a Linchpin:  An Efficient and Convergent Synthesis of Amphidinolide P
  作者：Barry M. Trost、Julien P. N. Papillon

  DOI：10.1021/ja045449x

  日期：2004.10.1

  A short and efficient synthesis of the cytotoxic macrolide amphidinolide P is described. A remarkably chemo- and regioselective ruthenium-catalyzed alkene-alkyne coupling allows for a convergent synthesis and demonstrates that both enynes and beta-lactones are suitable coupling partners. This work also features a novel strategy for the preparation of macrolactones via intramolecular transesterification of beta-lactones. The target structure was prepared in 15 steps for the longest linear sequence and 10% overall yield, 24 steps total.
• Two Ene–Yne Metathesis Approaches to the Total Synthesis of Amphidinolide P
  作者：Edgars Jecs、Steven T. Diver

  DOI：10.1021/acs.orglett.5b01601

  日期：2015.7.17

  The total synthesis of amphidinolide P was achieved through two different ene-yne metathesis, approaches. In each approach, the metathesis step was performed at late stages in the synthesis with all other functionality present. By forging two successful pathways to the synthesis of 1, some of the strengths and weaknesses of metathesis-intensive synthetic strategies were identified.