Monocillin II | 853798-66-0

• 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: Monocillin II
• 英文别名: (4R,6E,10E)-16,18-dihydroxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,10,15,17-pentaene-2,12-dione
• CAS: 853798-66-0
• 化学式: C₁₈H₂₀O₅
• 分子量: 316.354
• InChiKey: AGKSYPMAQRUJJY-RNLVMQRLSA-N

物化性质

• 熔点：
  188-191 °C(Solv: acetone (67-64-1))
• 沸点：
  599.0±50.0 °C(Predicted)
• 密度：
  1.190±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Monocillin II 在 5%-palladium/activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.5h， 以74.7%的产率得到lasicicol
  参考文献：
  名称：

  Synthesis and structure–activity relationships of radicicol derivatives and WNT-5A expression inhibitory activity

  摘要：

  WNT-5A, a secretory glycoprotein, is related to the proliferation of dermal papilla cells. To develop a hair-growth stimulant, we have been searching for inhibitors of WNT-5A expression. We identified radicicol (1) as an active compound, and synthesized several radicicol derivatives. Among them, 6,7-dihydro-10 alpha-hydroxy radicicol (31) was found to function as a new potent WNT-5A expression inhibitor with relatively low toxicity and excellent stability. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.04.060
• 作为产物：
  描述：

  (R)-(-)-4-烯基-2-戊醇 在 sulfonic acid resin MP 、 四丁基碘化铵 ethoxycarbonylazocarboxymethyl polystyrene 、 三(3-氯苯基)膦 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.67h， 生成 Monocillin II
  参考文献：
  名称：

  方向性的软骨素合成和针对一组激酶的生物学评估。

  摘要：

  Pochonins AF最近被表征为自然存在的14元间苯二酸内酯家族的6个新成员。由于天然间苯二酚内酯中存在大量的ATPase和激酶抑制剂，因此建立了基于软骨素支架的文库，该文库具有五个多样性点，其中包括超出天然类似物的多样性。该文库是通过使用适合自动化的固体支持试剂合成的。测试该文库在10 microM下对一组24种激酶的抑制作用后，命中率> 14％。这些结果证明了间苯二酚对抑制治疗相关激酶的潜力。

  DOI：

  10.1002/chem.200600553

文献信息

• Macrocyclic compounds useful as inhibitors of kinases and HSP90
  申请人：Winssinger Nicolas

  公开号：US20080146545A1

  公开（公告）日：2008-06-19

  Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

  本发明公开了式I-V的大环化合物，它们是pochonin邻苯二酚内酯的类似物，并公开了制备这些化合物的方法。所公开的化合物可用作激酶和热休克蛋白90（HSP 90）的抑制剂。还公开了包含有效的激酶抑制剂量或有效的HSP90抑制剂量的药物组合物以及治疗由激酶和HSP90介导的疾病的方法。
• MACROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF KINASES AND HSP90
  申请人：WINSSINGER Nicolas

  公开号：US20120077775A1

  公开（公告）日：2012-03-29

  Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

  本发明公开了式I-V的大环化合物，它们是pochonin酚羧酸内酯的类似物，并公开了制备这些化合物的方法。所公开的化合物可用作激酶和热休克蛋白90（HSP90）的抑制剂。还公开了含有有效的激酶抑制剂量或有效的HSP90抑制剂量的药物组合物以及治疗由激酶和HSP90介导的疾病的方法。
• Treatment Of Neurofibromatosis With Radicicol And Its Derivatives
  申请人：CHEN Ruihong

  公开号：US20100292218A1

  公开（公告）日：2010-11-18

  The present invention provides compounds of formulae Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va and the therapeutic use thereof. The present invention also includes methods of treating NF2-deficient or NF1-deficient cells or neurodegenerative diseases with radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va. Furthermore, the present invention is directed to methods of inhibiting the growth of NF2-deficient or NF1-deficient tumors. The methods comprise contacting NF2-deficient or NF1-deficient tumor cells with radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va. The present invention is also directed to the combinational use of radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia′, IIa, IIa′, IIIa, IIIa′, IVa, or Va with at least one additional active agent, such as one or more HSP90 inhibitors.

  本发明提供了Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va配方的化合物及其治疗用途。本发明还包括使用紫霉素或其衍生物，例如公式I、II、III、IV、V、Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va中的一个或多个化合物，治疗NF2缺陷或NF1缺陷细胞或神经退行性疾病的方法。此外，本发明还涉及抑制NF2缺陷或NF1缺陷肿瘤生长的方法。该方法包括使用紫霉素或其衍生物，例如公式I、II、III、IV、V、Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va中的一个或多个化合物接触NF2缺陷或NF1缺陷肿瘤细胞。本发明还涉及紫霉素或其衍生物，例如公式I、II、III、IV、V、Ia、Ia′、IIa、IIa′、IIIa、IIIa′、IVa或Va与至少一种其他活性剂，例如一种或多种HSP90抑制剂的联合使用。
• Total synthesis of 14-membered ring β-resorcylic acid lactone (+)-monocillin II
  作者：Naoki Kokaji、Naru Ishikura、Akinobu Matsuzawa、Shogo Kamo、Kazuyuki Sugita

  DOI：10.1039/d4ob00110a

  日期：——

  This study outlines the total synthesis of (+)-monocillin II, wherein a cis-isomer selectively produces a trans-isomer during the ring-closing metathesis. The Mitsunobu reaction conducted at −60 °C, facilitating the formation of an ester bond, was the key to completing the total synthesis, which was accomplished in the longest linear sequence of 10 steps with an overall yield of 9.3%.

  本研究概述了 (+)-莫诺西林 II 的全合成，其中顺式异构体在闭环复分解过程中选择性地产生反式异构体。在-60℃下进行的Mitsunobu反应促进了酯键的形成，是完成全合成的关键，该反应以最长的10步线性序列完成，总产率为9.3%。
• WO2008/21213
  申请人：——

  公开号：——

  公开（公告）日：——