(+)-hemi-phorboxazole A | 1140233-69-7

• 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: (+)-hemi-phorboxazole A
• 英文别名: (E)-3-[(1R,6E,9R,11R,12R,13S,16Z,19S,23R,25S,27R,31S)-27-hydroxy-12,31-dimethyl-21-methylidene-15-oxo-4,10,14,29,30-pentaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-11-yl]but-2-enenitrile
• CAS: 1140233-69-7
• 化学式: C₃₃H₄₂N₂O₇
• 分子量: 578.706
• InChiKey: YTQSRBIUUZXQQA-YKQFKUJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  42
• 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：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (1R,6E,9R,11R,12R,13S,16Z,19S,23R,25R,27R,31S)-27-[tert-butyl(dimethyl)silyl]oxy-11-[(E)-1-iodoprop-1-en-2-yl]-12,31-dimethyl-21-methylidene-4,10,14,29,30-pentaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one 在 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 苯 为溶剂， 生成 (+)-hemi-phorboxazole A
  参考文献：
  名称：

  佛盒唑合成研究：佛盒唑 A 和半佛盒唑 A 相关类似物的设计、合成和生物学评价

  摘要：

  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。

  DOI：

  10.1016/j.tet.2010.12.043

文献信息

• [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。
• Hemi-Phorboxazole A: Structure Confirmation, Analogue Design and Biological Evaluation
  作者：Amos B. Smith、Zhuqing Liu、Anne-Marie L. Hogan、Doralyn S. Dalisay、Tadeusz F. Molinski

  DOI：10.1021/ol9014317

  日期：2009.8.20

  A synthesis providing totally synthetic (+)-hemi-phorboxazole A (1), proceeding in two steps (85% yield) from known vinyl iodide precursor (+)-2, has been achieved in conjunction with the design, synthesis, and biological evaluation of two hemi-phorboxazole analogues [(+)-3 and (-)-4] featuring ring replacements inscribed within the macrolide. Although hemi-phorboxazole A (1) displayed no activity when tested against Candida albicans and two human cancer cell lines, analogue (-)-4 exhibited significant tumor cell growth inhibitory activity in the nanomolar range against HCT-116 (colon) and SK-BR-3 (breast), while (+)-3 displayed promising antifungal activity against C. albicans.
• HEMI-PHORBOXAZOLE A DERIVATIVES AND METHODS OF THEIR USE
  申请人：Smith, III Amos B.

  公开号：US20130030027A1

  公开（公告）日：2013-01-31

  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 —C 1-6 alkyl; 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.
• US8957097B2
  申请人：——

  公开号：US8957097B2

  公开（公告）日：2015-02-17
• 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。