C(41)-methyl amphotericin B | 136255-45-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: C(41)-methyl amphotericin B
• 英文别名: 16-descarboxyl-16-methyl-amphotericin B；(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18,36-tetramethyl-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaen-13-one
• CAS: 136255-45-3
• 化学式: C₄₇H₇₅NO₁₅
• 分子量: 894.11
• InChiKey: WYNBQANSTFJJSC-YFOXDLFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  63
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  282
• 氢给体数：
  11
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  在 哌啶 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 3.0h， 以4 mg的产率得到C(41)-methyl amphotericin B
  参考文献：
  名称：

  A Post-PKS Oxidation of the Amphotericin B Skeleton Predicted to be Critical for Channel Formation Is Not Required for Potent Antifungal Activity

  摘要：

  The clinically vital antimycotic agent amphotericin B represents the archetypal example of a channel-forming small molecule. The leading model for self-assembly of the amphotericin B channel predicts that the C(41) carboxylate and the C(3') ammonium ions form intermolecular salt bridges/hydrogen bonds that are critical for stability. We herein report a flexible degradative synthesis pathway that enables the removal of either or both of these groups from amphotericin B. We further demonstrate with extensive NMR experiments that deleting these groups does not alter the conformation of the polyene macrolide skeleton. As predicted by the leading model, amphotericin B derivatives lacking the mycosamine sugar that contains the C(3') ammonium ion are completely inactive against Saccharomyces cerevisiae. However, strikingly-and in strong contradiction with the current model-the amphotericin B derivative lacking the C(41) carboxylate is at least equipotent to the natural product. Collectively, these findings demonstrate that the leading model for the mechanism of action of amphotericin B must be significantly revised-either the C(41) carboxylate is not required for channel formation or channel formation is not required for antifungal activity.

  DOI：

  10.1021/ja075739o

文献信息

• A Post-PKS Oxidation of the Amphotericin B Skeleton Predicted to be Critical for Channel Formation Is Not Required for Potent Antifungal Activity
  作者：Daniel S. Palacios、Thomas M. Anderson、Martin D. Burke

  DOI：10.1021/ja075739o

  日期：2007.11.1

  The clinically vital antimycotic agent amphotericin B represents the archetypal example of a channel-forming small molecule. The leading model for self-assembly of the amphotericin B channel predicts that the C(41) carboxylate and the C(3') ammonium ions form intermolecular salt bridges/hydrogen bonds that are critical for stability. We herein report a flexible degradative synthesis pathway that enables the removal of either or both of these groups from amphotericin B. We further demonstrate with extensive NMR experiments that deleting these groups does not alter the conformation of the polyene macrolide skeleton. As predicted by the leading model, amphotericin B derivatives lacking the mycosamine sugar that contains the C(3') ammonium ion are completely inactive against Saccharomyces cerevisiae. However, strikingly-and in strong contradiction with the current model-the amphotericin B derivative lacking the C(41) carboxylate is at least equipotent to the natural product. Collectively, these findings demonstrate that the leading model for the mechanism of action of amphotericin B must be significantly revised-either the C(41) carboxylate is not required for channel formation or channel formation is not required for antifungal activity.