(2S,4aR,6'S,8aR)-6'-((E)-2,6-dimethylhepta-1,6-dien-1-yl)-4,7-dimethyl-4'-methylene-3',4a,4',5,5',6'-hexahydrospiro[chromene-2,2'-pyran]-6(8aH)-one | 1376709-24-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2S,4aR,6'S,8aR)-6'-((E)-2,6-dimethylhepta-1,6-dien-1-yl)-4,7-dimethyl-4'-methylene-3',4a,4',5,5',6'-hexahydrospiro[chromene-2,2'-pyran]-6(8aH)-one
• 英文别名: (2S,4aR,6'S,8aR)-6'-[(1E)-2,6-dimethylhepta-1,6-dienyl]-4,7-dimethyl-4'-methylidenespiro[5,8a-dihydro-4aH-chromene-2,2'-oxane]-6-one
• CAS: 1376709-24-8
• 化学式: C₂₅H₃₄O₃
• 分子量: 382.543
• InChiKey: XSGLCVZMFOJFDS-CUAGPSTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (S,E)-3-((tert-butyldimethylsilyl)oxy)-1-((R)-4-isopropyl-2-thioxothiazolidin-3-yl)-5,9-dimethyldeca-4,9-dien-1-one 在 N-溴代丁二酰亚胺(NBS) 、 samarium diiodide 、 cerium(III) chloride heptahydrate 、 四丁基氟化铵 、 potassium carbonate 、 对甲苯磺酸 、 methyloxirane 、 sodium iodide 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 丙酮 、 正戊烷 为溶剂， 反应 13.75h， 生成 (2S,4aR,6'S,8aR)-6'-((E)-2,6-dimethylhepta-1,6-dien-1-yl)-4,7-dimethyl-4'-methylene-3',4a,4',5,5',6'-hexahydrospiro[chromene-2,2'-pyran]-6(8aH)-one
  参考文献：
  名称：

  Total Synthesis of the Potent cAMP Signaling Agonist (−)-Alotaketal A

  摘要：

  We have developed a convergent synthetic route to the potent cAMP signaling agonist (-)-alotaketal A that employs two stages of SmI2-mediated reductive allylation reactions for assembling the polycycle and fragment coupling. Also notable are a Hg(OAc)(2)-mediated selective alkene oxidation and the subtlety of the formation of the unprecedented spiroketal ring system. The probes AKAR4 and ICUE3 were used to evaluate the cAMP singaling agonistic activity of (-)-alotaketal A and elucidate its structure-activity relationship.

  DOI：

  10.1021/ja303529z

文献信息

• Total synthesis and structure–activity relationship study of the potent cAMP signaling agonist (−)-alotaketal A
  作者：Jinhua Huang、Jessica R. Yang、Jin Zhang、Jiong Yang

  DOI：10.1039/c3ob40120k

  日期：——

  A detailed account of the first total synthesis of alotaketal A, a tricyclic spiroketal sesterterpenoid that potently activates the cAMP signaling pathway, is provided. The synthesis employs both intra- and intermolecular reductive allylation of esters for assembling one of the fragments and their coupling. A Hg(OAc)2-mediated allylic mercuration is used to introduce the C22-hydroxyl group. The subtle influence of substituents over the course of the spiroketalization process is revealed. The synthesis confirms the relative and absolute stereochemistry of (−)-alotaketal A and allows verification of alotaketal A's effect over cAMP signaling using reporter-based FRET imaging assays with HEK 293T cells. Our studies also revealed alotaketal A's unique activity in selectively targeting nuclear PKA signaling in living cells.

  提供了对alotaketal A的首次完全合成的详细描述。alotaketal A是一种三环螺烯糖甙类化合物，能够有效激活cAMP信号通路。该合成采用了酯的分子内和分子间还原烯丙基化反应来组装其中一个片段及其耦合。通过Hg(OAc)2介导的烯丙基汞化反应引入了C22-羟基。合成过程中取代基的微妙影响被揭示出来。此合成确认了(−)-alotaketal A的相对和绝对立体化学，并可以使用HEK 293T细胞的报告基FRET成像实验验证alotaketal A对cAMP信号的影响。我们的研究还揭示了alotaketal A在活细胞中选择性靶向核PKA信号的独特活性。