(+)-cacospongionolide B

• 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: (+)-cacospongionolide B
• 英文别名: cacospongionolide B；3-[(2R)-5-[2-[(1S,2S,4aR,8aR)-1,2,4a-trimethyl-5-methylidene-3,4,6,7,8,8a-hexahydro-2H-naphthalen-1-yl]ethyl]-3,6-dihydro-2H-pyran-2-yl]-2-hydroxy-2H-furan-5-one
• 化学式: C₂₅H₃₆O₄
• 分子量: 400.558
• InChiKey: CVAZWHZRZNYCOV-UEJZYZGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲氧基-三氟甲基苯 、 (+)-cacospongionolide B 在 吡啶 作用下， 反应 2.0h， 以3 mg的产率得到(S)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionic acid (R)-5-oxo-3-{(R)-5-[2-((1S,2S,4aR,8aR)-1,2,4a-trimethyl-5-methylene-decahydro-naphthalen-1-yl)-ethyl]-3,6-dihydro-2H-pyran-2-yl}-2,5-dihydro-furan-2-yl ester
  参考文献：
  名称：

  A New Cacospongionolide Inhibitor of Human Secretory Phospholipase A₂ from the Tyrrhenian Sponge Fasciospongia cavernosa and Absolute Configuration of Cacospongionolides

  摘要：

  A new inhibitor of human secretory phospholipase A(2) (PLA(2)), cacospongionolide E (4a), has been isolated from the Tyrrhenian sponge Fasciospongia cavernosa. The structure was proposed on the basis of spectroscopic data and by chemical transformations. The absolute configuration of cacospongionolides 2a-4a was established using the modified Mosher's method. Cacospongionolide E was the most potent inhibitor toward human synovial PLA(2), showing higher potency than the reference compound manoalide and exerting no signs of toxicity on human neutrophils. It showed high activity in the Artemia salina bioassay and moderate toxicity in the fish (Gambusia affinis) lethality assay.

  DOI：

  10.1021/np980122t
• 作为产物：
  描述：

  3-糠醛 在 Grubbs catalyst first generation 、 di-μ-chloro-bis(1,5-cyclooctadiene)dirhodium 盐酸 、 4-二甲氨基吡啶 、 lithium hydroxide 、 氨 、 氢气 、 氧气 、 lithium 、 rose bengal 、 sodium hydride 、 (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 、 叔丁醇 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， -78.0~75.0 ℃ 、303.98 kPa 条件下， 反应 212.5h， 生成 (+)-cacospongionolide B
  参考文献：
  名称：

  Total Syntheses of (+)- and (−)-Cacospongionolide B, Cacospongionolide E, and Related Analogues. Preliminary Study of Structural Features Required for Phospholipase A₂ Inhibition

  摘要：

  The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide B and E are described. The pivotal steps in the synthetic route include a three-step sequence that couples the two main regions of the natural product, as well as generates the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A(2) suggests that the cacospongionolides have enantiospecific interactions with the enzyme that may be independent of the gamma-hydroxybutenolide moiety.

  DOI：

  10.1021/jo049285e

文献信息

• Methods and reagents for the treatment of immunoinflammatory disorders
  申请人：Manivasakam Palaniyandi

  公开号：US20050271661A1

  公开（公告）日：2005-12-08

  The invention involves the treatment, prevention, and reduction of immunoinflammatory disorders involving the combination of an agent that increases the signal activity of a glucocorticoid receptor (e.g., glucocorticoid receptor agonist) and an agent that modulates the signaling activity of one or more signaling pathways selected from the NF-κB pathway, NFAT pathway, AP-1 pathway, and Elk-1 pathway such that proinflammatory cytokine secretion or production, or any other inflammatory response, is reduced. Further, screening methods are provided for identifying candidate compounds and strategies useful for treating, preventing, or reducing such conditions.

  本发明涉及免疫炎症性疾病的治疗、预防和减轻，包括将增加糖皮质激素受体信号活性的制剂（如糖皮质激素受体激动剂）和调节选自NF-κB通路、NFAT通路、AP-1通路和Elk-1通路的一种或多种信号通路的信号活性的制剂结合使用，从而减少促炎细胞因子的分泌或产生，或任何其他炎症反应。此外，还提供了用于识别候选化合物以及治疗、预防或减轻此类病症的策略的筛选方法。
• Novel pathways in the etiology of cancer
  申请人：Benz C. Christopher

  公开号：US20060024691A1

  公开（公告）日：2006-02-02

  This invention pertains to the identification of two novel epithelial signaling pathways in ER-positive breast cancer s and the discovery that the cellular biology and (likely also the clinical outcome) of ER-positive breast cancer cells is unexpectedly altered when these signaling pathways are activated. The first pathway pertains to the discovery that NF-κB activation and/or DNA binding is implicated in the etiology of ER-positive breast (and other) cancers. The second pathway involves ligand-independent quinine-mediated ER activation by posphorylation (e.g. on SER-118 and SER-167 residues of ER) and nuclear translocation of full-length (67 kDA) ER as well as the phorphorylating activation of a truncated and nuclear-localized ER variant (˜52 kDa).

  本发明涉及在ER阳性乳腺癌中发现两种新型上皮信号通路，并发现当这些信号通路被激活时，ER阳性乳腺癌细胞的细胞生物学特性和（可能还有临床结果）会发生意想不到的改变。第一条途径是发现 NF-κB 激活和/或 DNA 结合与 ER 阳性乳腺癌（和其他癌症）的病因有关。第二种途径涉及与配体无关的奎宁介导的ER激活，即ER的正理论化（如ER的SER-118和SER-167残基）和全长（67 kDA）ER的核转位，以及截短的核定位ER变体（˜52 kDa）的正理论化激活。
• Total Syntheses of (+)- and (−)-Cacospongionolide B:  New Insight into Structural Requirements for Phospholipase A₂ Inhibition
  作者：Atwood K. Cheung、Marc L. Snapper

  DOI：10.1021/ja026899x

  日期：2002.10.1

  The first total synthesis of the antiinflammatory marine sponge metabolite (+)-cacospongionolide B has been accomplished in 12 linear steps. The pivotal transformations include a three-step sequence coupling the two main regions of the natural product as well as generating the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A(2) suggests that cacospongionolide B has an enantiospecific interaction with the enzyme that is independent of the gamma-hydroxybutenolide moiety.
• METHODS AND REAGENTS FOR THE TREATMENT OF IMMUNOINFLAMMATORY DISORDERS
  申请人：CombinatoRx, Incorporated

  公开号：EP1781267A2

  公开（公告）日：2007-05-09
• EP1781267A4
  申请人：——

  公开号：EP1781267A4

  公开（公告）日：2009-03-11