(1S,6E,9R,11R,12R,13S,16Z,19S,23R,25S,31S)-11-[(E)-1-iodoprop-1-en-2-yl]-12,31-dimethyl-21-methylidene-4,10,14,28,29,30-hexaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one | 879872-47-6

• 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: (1S,6E,9R,11R,12R,13S,16Z,19S,23R,25S,31S)-11-[(E)-1-iodoprop-1-en-2-yl]-12,31-dimethyl-21-methylidene-4,10,14,28,29,30-hexaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one
• CAS: 879872-47-6
• 化学式: C₃₁H₄₀INO₇
• 分子量: 665.566
• InChiKey: IFXOFQYJJQXPOG-XDRFFJLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  40
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (1S,6E,9R,11R,12R,13S,16Z,19S,23R,25S,31S)-11-[(E)-1-iodoprop-1-en-2-yl]-12,31-dimethyl-21-methylidene-4,10,14,28,29,30-hexaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 三苯胂 、 四丁基氟化铵 、 N,N-二异丙基乙胺 、 Tetrabutylammoniumsalz der Diphenylphosphinsaeure 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 C₅₂H₆₈N₂O₁₃
  参考文献：
  名称：

  Design and Synthesis of a Potent Phorboxazole C(11−15) Acetal Analogue

  摘要：

  We disclose here the design, synthesis, and biological evaluation of simplified Z- and E-C(2-3) alkynyl phorboxazole C(11-15) acetals (+)-7Z and (+)-7E, wherein the Z-isomer proved to be a potent nanomolar cytotoxic agent. Reevaluation of (+)-C(45-46) E-chloroalkenyl phorboxazole A (6) confirms subnanomolar activity across a broad panel of human cancer cell lines.

  DOI：

  10.1021/ol060014v
• 作为产物：
  描述：

  (3S)-4-[(2R,6R)-6-[2-[tert-butyl(diphenyl)silyl]oxyethyl]-4-methylideneoxan-2-yl]butane-1,3-diol 在 phosphate buffer 、 18-冠醚-6 、 三丁基膦 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 40.92h， 生成 (1S,6E,9R,11R,12R,13S,16Z,19S,23R,25S,31S)-11-[(E)-1-iodoprop-1-en-2-yl]-12,31-dimethyl-21-methylidene-4,10,14,28,29,30-hexaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one
  参考文献：
  名称：

  Design and Synthesis of a Potent Phorboxazole C(11−15) Acetal Analogue

  摘要：

  We disclose here the design, synthesis, and biological evaluation of simplified Z- and E-C(2-3) alkynyl phorboxazole C(11-15) acetals (+)-7Z and (+)-7E, wherein the Z-isomer proved to be a potent nanomolar cytotoxic agent. Reevaluation of (+)-C(45-46) E-chloroalkenyl phorboxazole A (6) confirms subnanomolar activity across a broad panel of human cancer cell lines.

  DOI：

  10.1021/ol060014v

文献信息

• Phorboxazole compounds and methods of their preparation
  申请人：The Trustees of the University of Pennsylvania

  公开号：US07485631B2

  公开（公告）日：2009-02-03

  Novel macrolactone compounds, their methods of preparation, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the macrolactone compounds may be useful, inter alia, for treating various cancers, inducing apoptosis in malignant cells, or inhibiting cancer cell division.

  新型大环内酯化合物，其制备方法，含有这些化合物的药物组合物，以及这些药物的药用方法被披露。在某些实施例中，这些大环内酯化合物可能有助于治疗各种癌症，诱导恶性细胞凋亡，或抑制癌细胞分裂。
• [EN] HEMI-PHORBOXAZOLE A DERIVATIVES AND METHODS OF THEIR USE<br/>[FR] DÉRIVÉS DE L'HÉMI-PHORBOXAZOLE A ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV PENNSYLVANIA

  公开号：WO2011011665A1

  公开（公告）日：2011-01-27

  The present invention is directed to hemi phorboxazole A: and its stereoisomers, as well as derivatives of hemi phorboxazole A of formula I: wherein ring A is aryl or a 5- or 6-membered heteroaryl optionally substituted with one or more of halogen, -OH, or -C1-6alkyl; and R is-CN, a 5- or 6-membered heteroaryl, or halogen; and the pharmaceutically acceptable salt forms thereof, in addition to methods of using these compounds.

  本发明涉及半磷酸酯A及其立体异构体，以及公式I中的半磷酸酯A的衍生物：其中环A是芳基或5-或6-成员杂芳基，可以选择地被一个或多个卤素，-OH或-C1-6烷基取代；R是-CN，5-或6-成员杂芳基，或卤素；以及其药用盐形式，以及使用这些化合物的方法。
• Phorboxazole synthetic studies: design, synthesis and biological evaluation of phorboxazole A and hemi-phorboxazole A related analogues
  作者：Amos B. Smith、Anne-Marie L. Hogan、Zhuqing Liu、Thomas M. Razler、Regina M. Meis、Brandon I. Morinaka、Tadeusz F. Molinski

  DOI：10.1016/j.tet.2010.12.043

  日期：2011.7

  evaluation of a new phorboxazole analogue, comprising an acetal replacement for the C-ring tetrahydropyran of the natural product and carrying a potency-enhancing C(45–46) vinyl chloride side chain, is described. In addition, the synthesis of (+)-hemi-phorboxazole A and a series of related hemi-phorboxazole A analogues has been achieved. The new acetal ring replacement analogue displayed activity comparable

  描述了一种新的佛波唑类似物的设计、合成和生物学评价，该类似物包含天然产物C环四氢吡喃的缩醛替代物，并带有增强效力的 C(45-46) 氯乙烯侧链。此外，还实现了(+)-半佛盒唑A和一系列相关的半佛盒唑A类似物的合成。新的缩醛环替代类似物显示出与母体天然产物对 HCT-116（结肠）细胞的活性相当（IC 50 2.25 ng/mL）。同样重要的是，佛盒唑类似物和两个相关的半佛盒唑 A 同源物在针对致病性白色念珠菌菌株进行检测时表现出显着的抗真菌活性。
• Synthesis and Biological Evaluation of Phorboxazole Congeners Leading to the Discovery and Preparative-Scale Synthesis of (+)-Chlorophorboxazole A Possessing Picomolar Human Solid Tumor Cell Growth Inhibitory Activity
  作者：Amos B. Smith、Thomas M. Razler、Regina M. Meis、George R. Pettit

  DOI：10.1021/jo701816h

  日期：2008.2.1

  Highly convergent syntheses of eight phorboxazole congeners and their evaluation against a diverse panel of human solid tumor cancer cell lines have been achieved. Specifically, the C(45-46) alkyne, alkene, and alkane phorboxazole A analogues [(+)-4-(+)-6] were constructed and found to display single digit nanomolar cell growth inhibitory activities in a series of human cancer cell lines. The structurally simplified C(11-15)-acetal congener (+)-20Z also proved potent albeit reduced (cf. 34.6 nM) when evaluated against the same cell line panel. Importantly, (+)-C(46)-chlorophorboxazole A (3) displayed picomolar (pM) inhibitory activity in several cell lines.
• Phorboxazole Compounds and Methods of Their Preparation
  申请人：Razler Thomas M.

  公开号：US20090163563A1

  公开（公告）日：2009-06-25

  Novel macrolactone compounds, their methods of preparation, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the macrolactone compounds may be useful, inter alia, for treating various cancers, inducing apoptosis in malignant cells, or inhibiting cancer cell division.