5-O-tert-butyldimethylsilylavermectin B_1a aglycone | 73162-84-2

• 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: 5-O-tert-butyldimethylsilylavermectin B_1a aglycone
• 英文别名: avermectin B_1a aglycon 5-tert-butyldimethylsilyl ether；5-O-(tert-butyldimethylsilyl)avermectin B₁ aglycon；(1'R,2R,3S,4'S,6S,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-2-[(2S)-butan-2-yl]-21'-[tert-butyl(dimethyl)silyl]oxy-12',24'-dihydroxy-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one
• CAS: 73162-84-2
• 化学式: C₄₀H₆₂O₈Si
• 分子量: 699.013
• InChiKey: ZXKHDGJUNUABPF-MCWKAOPLSA-N

物化性质

• 沸点：
  771.1±60.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.34
• 重原子数：
  49
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-O-tert-butyldimethylsilylavermectin B_1a aglycone 在 4 A molecular sieve 、 silver trifluoromethanesulfonate 、 氟化氢吡啶 作用下， 以 吡啶 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 30.33h， 生成 阿维菌素
  参考文献：
  名称：

  Total Synthesis of the Antiparasitic Agent Avermectin B1a

  摘要：

  The synthesis of avermectin B-1a has been completed by a route that assembles the aglycon from three subunits consisting of the hexahydrobenzofuran moiety (A), the spiroketal segment (B), and the acyclic portion (C) comprising C9-C15. Connection is made in a B + C --> (B - C) + A sequence, and the synthesis is concluded by attachment to the aglycon of the L-oleandrosyl-L-oleandrose disaccharide via the pyridylthio glycoside.

  DOI：

  10.1021/ja00112a006
• 作为产物：
  描述：

  在 咪唑 、 氢氟酸 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 111.0h， 生成 5-O-tert-butyldimethylsilylavermectin B_1a aglycone
  参考文献：
  名称：

  Total Synthesis of the Antiparasitic Agent Avermectin B1a

  摘要：

  The synthesis of avermectin B-1a has been completed by a route that assembles the aglycon from three subunits consisting of the hexahydrobenzofuran moiety (A), the spiroketal segment (B), and the acyclic portion (C) comprising C9-C15. Connection is made in a B + C --> (B - C) + A sequence, and the synthesis is concluded by attachment to the aglycon of the L-oleandrosyl-L-oleandrose disaccharide via the pyridylthio glycoside.

  DOI：

  10.1021/ja00112a006

文献信息

• Synthesis, biological activities and structure−activity relationships for new avermectin analogues
  作者：Jian Zhang、Xiang Nan、Hai-Tao Yu、Pi-Le Cheng、Yan Zhang、Ying-Qian Liu、Shao-Yong Zhang、Guan-Fang Hu、Huanxiang Liu、An-Liang Chen

  DOI：10.1016/j.ejmech.2016.05.056

  日期：2016.10

  LC50 values of 7.744, 5.634, 6.809, 7.939 and 52.234 μM, respectively. Furthermore, QSAR analysis showed that the molecular shape, size, connectivity degree and electronic distribution of avermectin analogues had substantial effects on insecticidal potency. These preliminary results provided useful insight in guiding further modifications of avermectin in the development of potential new insecticides.

  为了发现具有良好杀虫活性的新分子，合成了40多种新的阿维菌素衍生物，并评估了它们对三种物种的蜘蛛，昆虫和线虫的生物活性，这些物种分别是朱砂叶螨（Tetranychus Cinnabarinus），蚜虫（Aphis craccivora）和松柏xylophilus。所有测试的化合物均显示出对三种昆虫的有效抑制活性。值得注意的是，大多数化合物对朱砂毛虫表现出高选择性，其中一些与阿维菌素相比具有更好的选择性。特别是化合物9j（LC 50：0.005μM）和16d（LC 50：0.002μM）对朱砂丁香的活性分别比阿维菌素（LC 50： 0.013μM ）高2.5倍和4.7倍。此外，化合物9B，9D-F ，9H，9J，9升，9N，9P，9R，9V和17D显示了优良的活性与LC 50个相比的2.959-5.013μM的值1（LC 50： 6.746μM）对乙。松材线虫。同时，化合物9f，9g，9h和9m的杀虫活性针对A
• Avermectin chemistry and action: ester- and ether-type candidate photoaffinity probes
  作者：Yoshihisa Tsukamoto、Loretta M. Cole、John E. Casida

  DOI：10.1016/s0968-0896(99)00259-x

  日期：2000.1

  Avermectin B-1a (1) is a potent anthelmintic, insecticide, miticide and chloride channel activator on interaction with a specific nerve membrane site analyzed by binding assays with [H-3]1. Candidate photoaffinity probes were prepared replacing the dioleandrosyl substituent with potential isosteric esters and ethers approximating the original overall atom length and terminating in a phenyl moiety substituted with azido, iodo or hydroxy. Several of the candidates met the goal of high potency on mouse, housefly and fruit fly brain chloride channels with IC50 values of 7-57 nM in competing for the [H-3]1 binding site. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Rapid Exploration of Novel Anthelmintic Agents from Alkyne-Bearing Avermectin Derivatives via Click Chemistry
  作者：Toshiaki Sunazuka、Tomoyasu Hirose、Akari Ikeda、Ayumi Tsutsui、Satoshi Ōmura

  DOI：10.3987/com-19-s(f)18

  日期：——

  We applied copper-catalyzed 1,4-disubstituted-1,2,3-triazole formation, a major connective reaction in "Click Chemistry", to synthesize novel avermectin derivatives. Among the synthetic triazole-containing avermectins, the 4-hydroxybutyltriazole derivative (3a) was found to demonstrate notable antinematodal activity against ivermectin-resistant Trichinella spiralis in vitro. Furthermore, a new compound (3a) also exhibited strong antinematode properties against ivermectin-resistant Haemonchus contortus in sheep following oral administration.
• Synthesis and biological activity of 13-epi-avermectins: potent anthelmintic agents with an increased margin of safety
  作者：Timothy A. Blizzard、Gaye M. Margiatto、Helmut Mrozik、Wesley L. Shoop、Robert A. Frankshun、Michael H. Fisher

  DOI：10.1021/jm00099a014

  日期：1992.10

  Chemical conversion of the potent anthelmintic natural products avermectin B1 (1) and avermectin B2 (3) to the corresponding 13-epi analogs (15 and 9) is described. The novel analogs retain the full potency of the natural products but are substantially safer.
• Total Synthesis of the Antiparasitic Agent Avermectin B1a
  作者：James D. White、Gary L. Bolton、Anura P. Dantanarayana、Christina M. J. Fox、Roger N. Hiner、Randy W. Jackson、Kazuhiko Sakuma、Ulhas S. Warrier

  DOI：10.1021/ja00112a006

  日期：1995.2

  The synthesis of avermectin B-1a has been completed by a route that assembles the aglycon from three subunits consisting of the hexahydrobenzofuran moiety (A), the spiroketal segment (B), and the acyclic portion (C) comprising C9-C15. Connection is made in a B + C --> (B - C) + A sequence, and the synthesis is concluded by attachment to the aglycon of the L-oleandrosyl-L-oleandrose disaccharide via the pyridylthio glycoside.