28,29-didehydronystatin A1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 28,29-didehydronystatin A1
• 英文别名: S44HP；28,29-didehydronystatin A(1)；(1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2S,3R,4R,5R,6S)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
• 化学式: C₄₇H₇₃NO₁₇
• 分子量: 924.093
• InChiKey: GVMUFFMCUCUGSJ-UJMJZUPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  65
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  320
• 氢给体数：
  12
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  28,29-didehydronystatin A1 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氯化铵 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 1.25h， 生成 (1S,3R,4R,7R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2S,3R,4R,5R,6S)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxamide
  参考文献：
  名称：

  Chemical Modification and Biological Evaluation of New Semisynthetic Derivatives of 28,29-Didehydronystatin A₁ (S44HP), a Genetically Engineered Antifungal Polyene Macrolide Antibiotic

  摘要：

  Twenty-three new derivatives of the heptaene nystatin analogue 28,29-didehydronystatin A(1) (1) (S44HP) were obtained by chemical modification of C 16 carboxyl and amino groups of mycosamine. These derivatives comprised 15 carboxamides, 4 N-alkyl derivatives, 3 N-derivatives containing additional N-linked monosaccharide or disaccharide moiety (products of Amadori rearrangement), and 1 N-aminnoacyl derivative. The derivatives have been tested in vitro against yeasts Candida albicans, Cryptococcus humicolus, and filamentous fungi (molds) Aspergillus niger and Fusarum oxysporum, as well as for hemolytic activity against human erythrocytes. Structure-activity relationships for the compounds obtained are discussed. The most active and least hemolytic derivative 3-(N,N-dimethylamino)propylamide of S44HP (6) was tested for acute toxicity and antifungal activity in animal model. Whereas amphotericin B and S44HP were active in vivo at doses close to the maximal tolerated dose, 6 was considerably less toxic and more active compared to these two antibiotics.

  DOI：

  10.1021/jm800695k

文献信息

• Chemical Modification and Biological Evaluation of New Semisynthetic Derivatives of 28,29-Didehydronystatin A₁ (S44HP), a Genetically Engineered Antifungal Polyene Macrolide Antibiotic
  作者：Maria N. Preobrazhenskaya、Evgenia N. Olsufyeva、Svetlana E. Solovieva、Anna N. Tevyashova、Marina I. Reznikova、Yuryi N. Luzikov、Larisa P. Terekhova、Aleksei S. Trenin、Olga A. Galatenko、Ivan D. Treshalin、Elena P. Mirchink、Vladimir M. Bukhman、Håvard Sletta、Sergey B. Zotchev

  DOI：10.1021/jm800695k

  日期：2009.1.8

  Twenty-three new derivatives of the heptaene nystatin analogue 28,29-didehydronystatin A(1) (1) (S44HP) were obtained by chemical modification of C 16 carboxyl and amino groups of mycosamine. These derivatives comprised 15 carboxamides, 4 N-alkyl derivatives, 3 N-derivatives containing additional N-linked monosaccharide or disaccharide moiety (products of Amadori rearrangement), and 1 N-aminnoacyl derivative. The derivatives have been tested in vitro against yeasts Candida albicans, Cryptococcus humicolus, and filamentous fungi (molds) Aspergillus niger and Fusarum oxysporum, as well as for hemolytic activity against human erythrocytes. Structure-activity relationships for the compounds obtained are discussed. The most active and least hemolytic derivative 3-(N,N-dimethylamino)propylamide of S44HP (6) was tested for acute toxicity and antifungal activity in animal model. Whereas amphotericin B and S44HP were active in vivo at doses close to the maximal tolerated dose, 6 was considerably less toxic and more active compared to these two antibiotics.