11-desacetylwortmannin | 51819-63-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 11-desacetylwortmannin
• 英文别名: 11-O-desacetyl-wortmannin；(1R,3R,5S,9R,18S)-3-hydroxy-18-(methoxymethyl)-1,5-dimethyl-13,17-dioxapentacyclo[10.6.1.02,10.05,9.015,19]nonadeca-2(10),12(19),14-triene-6,11,16-trione
• CAS: 51819-63-7
• 化学式: C₂₁H₂₂O₇
• 分子量: 386.401
• InChiKey: SIROZWFVILRLGG-DZOAAFPKSA-N

物化性质

• 沸点：
  624.1±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  11-desacetylwortmannin 在 重铬酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以79%的产率得到11-Desacetoxy-11-oxo-wortmannin
  参考文献：
  名称：

  Synthesis and in Vitro Evaluation of New Wortmannin Esters:  Potent Inhibitors of Phosphatidylinositol 3-Kinase

  摘要：

  New C-11 esters of the fermentation product wortmannin have been synthesized, with some of them further derivatized at C-17. The new esters show greater inhibition of isolated phosphatidylinositol 3-kinase and increased cell cytotoxicity in a rapidly proliferating leukemia cell line, when compared to wortmannin. Reduction of the C-17 ketone caused a slight increase in activity, while acylation of this new alcohol caused severe loss of activity. With their increased activity, the new C-11 esters may be good candidates to explore the in vivo antitumor effects of phosphatidylinositol 3-kinase inhibitors.

  DOI：

  10.1021/jm960283z
• 作为产物：
  描述：

  11-O-desacetyl-20-(N,N-diethylimino)-20-desoxowortmannin 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 19.0h， 生成 11-desacetylwortmannin
  参考文献：
  名称：

  Synthesis and in Vitro Evaluation of New Wortmannin Esters:  Potent Inhibitors of Phosphatidylinositol 3-Kinase

  摘要：

  New C-11 esters of the fermentation product wortmannin have been synthesized, with some of them further derivatized at C-17. The new esters show greater inhibition of isolated phosphatidylinositol 3-kinase and increased cell cytotoxicity in a rapidly proliferating leukemia cell line, when compared to wortmannin. Reduction of the C-17 ketone caused a slight increase in activity, while acylation of this new alcohol caused severe loss of activity. With their increased activity, the new C-11 esters may be good candidates to explore the in vivo antitumor effects of phosphatidylinositol 3-kinase inhibitors.

  DOI：

  10.1021/jm960283z

文献信息

• WORTMANNIN-RAPALOG CONJUGATE AND USES THEREOF
  申请人：GU Jianxin

  公开号：US20080249124A1

  公开（公告）日：2008-10-09

  An anti-neoplastic wortmannin conjugate is described formed by a linking a rapalog and wortmannin. Such a linkage is removable following administration to a subject. Use of such a conjugate in an antineoplastic regimen is described.

  描述了一种抗肿瘤的沃特曼宾共轭物，由连接雷帕霉素和沃特曼宾形成。这种连接在给予受试者后可被移除。描述了在抗肿瘤疗法中使用这种共轭物的方法。
• WORTMANNIN-RAPAMYCIN CONJUGATE AND USES THEREOF
  申请人：GU JIANXIN

  公开号：US20080249123A1

  公开（公告）日：2008-10-09

  A rapamycin—wortmannin conjugate is described, in which the conjugate is formed by linking the rapamycin and wortmannin together in such a manner that the rapamycin and the wortmannin are separated following administration to a subject. Use of such a conjugate in an antineoplastic regimen is described.

  描述了一种雷帕霉素-沃特曼宾共轭物，其中共轭物通过将雷帕霉素和沃特曼宾连接在一起形成，以便在给予受试者后分离雷帕霉素和沃特曼宾。描述了在抗肿瘤方案中使用这种共轭物的方法。
• Water soluble wortmannin derivatives
  申请人：Wyeth Holdings Corporation

  公开号：US20040213757A1

  公开（公告）日：2004-10-28

  This invention relates to soluble derivatives of wortmannin that utilizes water-soluble polymers as carriers for a drug and includes compounds having the structures as described within the specification.

  这项发明涉及沃特曼宁的可溶性衍生物，利用水溶性聚合物作为药物的载体，并包括具有规范中描述的结构的化合物。
• Enantioselective Total Synthesis of (+)-Wortmannin
  作者：Yinliang Guo、Tianfei Quan、Yandong Lu、Tuoping Luo

  DOI：10.1021/jacs.7b02515

  日期：2017.5.24

  A concise and enantioselective total synthesis of the potent PI3K inhibitor (+)-wortmannin is described. A Pd-catalyzed cascade reaction was first developed to connect a synthon derived from Hajos-Parrish ketone to a furan moiety. The subsequent Friedel-Crafts alkylation of the β-position of a furan ring to an epoxide was optimized to establish the C10 quaternary center. (+)-Wortmannin was eventually

  描述了有效的 PI3K 抑制剂 (+)-渥曼青霉素的简洁和对映选择性全合成。最初开发了 Pd 催化的级联反应，以将衍生自 Hajos-Parrish 酮的合成子连接到呋喃部分。随后将呋喃环的 β 位变为环氧化物的 Friedel-Crafts 烷基化被优化以建立 C10 四元中心。(+)-渥曼青霉素最终通过呋喃烯丙基位置后期氧化后的转化来完成。对 17-β-羟基-渥曼青霉素和环氧化物类似物进行了激酶组分析和体外酶促测定。
• Synthesis of fluorescent derivatives of wortmannin and demethoxyviridin as probes for phosphatidylinositol 3-kinase
  作者：José-Luis Giner、Karen A Kehbein、James A. Cook、Michele C. Smith、Chris J. Vlahos、John A. Badwey

  DOI：10.1016/j.bmcl.2006.01.091

  日期：2006.5

  inhibitors, wortmannin and demethoxyviridin. The esterification of 11-deacetylwortmannin, 17-hydroxywortmannin, and demethoxyviridin with the fluorescent carboxylic acids NBD-sarcosine and 7-dimethylaminocoumarin-4-acetic acid generated six novel fluorescent esters. Potent inhibition of PI 3-kinase-alpha was observed for the derivatives of 11-desacetylwortmannin and demethoxyviridin.

  合成了有效的PI 3-激酶抑制剂渥曼青霉素和脱甲氧维他汀的荧光类似物。11-去乙酰基渥曼青霉素，17-羟基渥曼青霉素和去甲氧基维啶与荧光羧酸NBD-肌氨酸和7-二甲基氨基香豆素-4-乙酸的酯化反应生成了六种新颖的荧光酯。对于11-去乙酰基渥曼青霉素和去甲氧基维里汀的衍生物，观察到了对PI 3-激酶-α的强抑制作用。