resiniferonol 9,13,14-orthophenylacetate

• 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: resiniferonol 9,13,14-orthophenylacetate
• 英文别名: ROPA；(1R,2R,6R,10S,11R,15R,17R)-13-benzyl-6-hydroxy-8-(hydroxymethyl)-4,17-dimethyl-15-prop-1-en-2-yl-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-5-one
• 化学式: C₂₈H₃₂O₆
• 分子量: 464.558
• InChiKey: FFKXTXJQZGIKQZ-PBUCZTEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  resiniferonol 9,13,14-orthophenylacetate 在 六氯丙酮 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以87%的产率得到9,13,14-orthophenylacetylresiniferonyl 20-chloride
  参考文献：
  名称：

  Similarities and Differences in the Structure−Activity Relationships of Capsaicin and Resiniferatoxin Analogues

  摘要：

  Structure-activity relationships in analogues of the irritant natural product capsaicin have previously been rationalized by subdivision of the molecule into three structural regions (A, B, and C). The hypothesis that resiniferatoxin (RTX), which is a high-potency ligand for the same receptor and which has superficial structural similarities with capsaicin, could be analogously subdivided has been investigated. The effects of making parallel changes in the two structural series have been studied in a cellular functional assay which is predictive of analgesic activity. Parallel structural changes in the two series lead to markedly different consequences on biological activity; the 3- and 4-position aryl substituents (corresponding to the capsaicin 'A-region') which are strictly required for activity in capsaicin analogues are not important in RTX analogues. The homovanillyl C-20 ester group in RTX (corresponding to the capsaicin 'B-region') is more potent than the corresponding amide, in contrast to the capsaicin analogues. Structural variations to the diterpene moiety suggest that the functionalized 5-membered diterpene ring of RTX is an important structural determinant for high potency. Modeling studies indicate that the 3D position of the alpha-hydroxy ketone moiety in the 5-membered ring is markedly different in the phorbol (inactive) analogues and RTX (active) series. This difference appears to be due to the influence of the strained ortho ester group in RTX, which acts as a local conformational constraint. The reduced activity of an analogue substituted in this region and the inactivity of a simplified analogue in which this unit is entirely removed support this conclusion.

  DOI：

  10.1021/jm960139d
• 作为产物：
  描述：

  resiniferatoxin 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 resiniferonol 9,13,14-orthophenylacetate
  参考文献：
  名称：

  Adolf, W.; Hecker, E., Zeitschrift fur Naturforschung, B: Chemical Sciences, 1993, vol. 48, # 3, p. 364 - 368

  摘要：

  DOI：

文献信息

• Unified Total Syntheses of Rhamnofolane, Tigliane, and Daphnane Diterpenoids
  作者：Akira Hirose、Ayumu Watanabe、Kohei Ogino、Masanori Nagatomo、Masayuki Inoue

  DOI：10.1021/jacs.1c06450

  日期：2021.8.11

  ABC-ring 6 by detaching the three-carbon units and the oxygen-appended groups. Intermediate 6 with six stereocenters was assembled from four achiral fragments in 12 steps by integrating three powerful transformations, as follows: (i) asymmetric Diels–Alder reaction to induce formation of the C-ring; (ii) π-allyl Stille coupling reaction to set the trisubstituted E-olefin of the B-ring; and (iii) Eu(fod)3-promoted

  Rhamnofolane、tigliane 和 daphnane diterpenoids 是结构复杂的天然产物，具有多种氧官能团，使它们在合成上具有挑战性。虽然这些二萜类化合物共享一个5/7/6反式稠合环系统（ABC 环），但 C 环上 C13 和 C14 位的三碳取代以及附加的氧官能团在它们之间是不同的，占这些天然产物的不同生物活性。在这里，我们开发了一种新的、统一的策略，用于快速全合成这三个家族的五个代表性成员，crotophorbolone ( 1 )、langduin A ( 2 )、prostratin ( 3 )、resiniferatoxin ( 4 ) 和 tinyatoxin ( 5)）。逆合成，1 - 5分别简化为它们共同的ABC-环6通过卸下三碳单元和氧附属基团。具有六个立体中心的中间体6由四个非手性片段分 12 步通过整合三个强大的转换组装而成，如下所示：（i）不对称
• Structure–activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The side chain benzylic methylene
  作者：Giovanni Appendino、Abdellah Ech-Chahad、Alberto Minassi、Luciano De Petrocellis、Vincenzo Di Marzo

  DOI：10.1016/j.bmcl.2009.11.035

  日期：2010.1

  The side chain benzylic methylene is a critical element for the vanilloid activity of resiniferatoxin (2a, RTX), and introduction of branching, oxygen functions, or isosteric substitution at this center proved detrimental, with a decrease of potency of 2-3 orders of magnitude compared to the natural product. Conversely, only a modest erosion of activity was observed upon a-methylation and alpha-methylenation of the side chain. Surprisingly, introduction of an iodine atom in the guaiacyl moiety of the oxygen isoster 2h led to an unexpected and remarkable (> 1000-fold) increase of potency, affording 2i, a compound that outperforms RTX in terms of vanilloid agonism and represents the first one-digit picomolar ligand of a TRP channel discovered to date. (C) 2009 Elsevier Ltd. All rights reserved.
• Bisnorsesquiterpenoids from Euphorbia resinifera Berg. and an Expeditious Procedure to Obtain Resiniferatoxin from Its Fresh Latex
  作者：Ernesto Fattorusso、Virginia Lanzotti、Orazio Taglialatela-Scafati、Gian Cesare Tron、Giovanni Appendino

  DOI：10.1002/1099-0690(20021)2002:1<71::aid-ejoc71>3.0.co;2-c

  日期：2002.1

  The fresh latex of cultivated E. resinifera Berg. is a convenient source of the ultrapotent vanilloid resiniferatoxin, and a transesterification-reesterification procedure that substantially alleviates the hazards associated with the direct isolation of this obnoxious diterpenoid has been developed. Various known phorboid constituents of the diterpenoid fraction were obtained in pure form and have been spectroscopically characterized for the first time, while the non-diterpenoid fraction of the latex gave, besides some common triterpenoids, three new bisnorsesquiterpenes of the dihydroionol type. The structures of these compounds were established through a combination of spectroscopic data and chemical reactions.
• Similarities and Differences in the Structure−Activity Relationships of Capsaicin and Resiniferatoxin Analogues
  作者：Christopher S. J. Walpole、Stuart Bevan、Graham Bloomfield、Robin Breckenridge、Iain F. James、Timothy Ritchie、Arpad Szallasi、Janet Winter、Roger Wrigglesworth

  DOI：10.1021/jm960139d

  日期：1996.1.1

  Structure-activity relationships in analogues of the irritant natural product capsaicin have previously been rationalized by subdivision of the molecule into three structural regions (A, B, and C). The hypothesis that resiniferatoxin (RTX), which is a high-potency ligand for the same receptor and which has superficial structural similarities with capsaicin, could be analogously subdivided has been investigated. The effects of making parallel changes in the two structural series have been studied in a cellular functional assay which is predictive of analgesic activity. Parallel structural changes in the two series lead to markedly different consequences on biological activity; the 3- and 4-position aryl substituents (corresponding to the capsaicin 'A-region') which are strictly required for activity in capsaicin analogues are not important in RTX analogues. The homovanillyl C-20 ester group in RTX (corresponding to the capsaicin 'B-region') is more potent than the corresponding amide, in contrast to the capsaicin analogues. Structural variations to the diterpene moiety suggest that the functionalized 5-membered diterpene ring of RTX is an important structural determinant for high potency. Modeling studies indicate that the 3D position of the alpha-hydroxy ketone moiety in the 5-membered ring is markedly different in the phorbol (inactive) analogues and RTX (active) series. This difference appears to be due to the influence of the strained ortho ester group in RTX, which acts as a local conformational constraint. The reduced activity of an analogue substituted in this region and the inactivity of a simplified analogue in which this unit is entirely removed support this conclusion.
• Adolf, W.; Hecker, E., Zeitschrift fur Naturforschung, B: Chemical Sciences, 1993, vol. 48, # 3, p. 364 - 368
  作者：Adolf, W.、Hecker, E.

  DOI：——

  日期：——