nocathiacin I | 214044-52-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: nocathiacin I
• 英文别名: MJ347-81F4 A；N-(3-amino-3-oxoprop-1-en-2-yl)-2-[(1S,18S,21E,28S,29S,30S)-30-[(2S,4S,5R,6S)-5-(dimethylamino)-4-hydroxy-4,6-dimethyloxan-2-yl]oxy-9,52-dihydroxy-18-[(1R)-1-hydroxyethyl]-21-(1-methoxyethylidene)-16,19,26,31,42,46-hexaoxo-32,43,54-trioxa-3,13,23,49-tetrathia-7,17,20,27,45,51,52,55,56,57-decazadecacyclo[26.16.6.229,40.12,5.112,15.122,25.138,41.147,50.06,11.034,39]heptapentaconta-2(57),4,6,8,10,12(56),14,22(55),24,34(39),35,37,40,47,50-pentadecaen-8-yl]-1,3-thiazole-4-carboxamide
• CAS: 214044-52-7
• 化学式: C₆₁H₆₀N₁₄O₁₈S₅
• 分子量: 1437.56
• InChiKey: FFLJEMWVYVKPDW-UMNFMQIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  98
• 可旋转键数：
  9
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  586
• 氢给体数：
  10
• 氢受体数：
  30

反应信息

• 作为反应物：
  描述：

  nocathiacin I 在 吡啶 、 三氟乙酸酐 、 水 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 10.5h， 生成 nocathiacin acid
  参考文献：
  名称：

  WO2007/127136

  摘要：

  公开号：

文献信息

• Novel semi-synthetic nocathiacin antibiotics: synthesis and antibacterial activity of bis- and mono-O-alkylated derivatives
  作者：Alicia Regueiro-Ren、B.Narasimhulu Naidu、Xiaofan Zheng、Thomas W. Hudyma、Timothy P. Connolly、John D. Matiskella、Yunhui Zhang、Oak K. Kim、Margaret E. Sorenson、Michael Pucci、Junius Clark、Joanne J. Bronson、Yasutsugu Ueda

  DOI：10.1016/j.bmcl.2003.09.061

  日期：2004.1

  rotection strategy was developed for the preparation of mono-O-alkyl hydroxypyridine analogues 5a,b. Most of the bis- and mono-O-alkyl nocathiacins maintained good in vitro activity but showed reduced in vivo efficacy when compared with the natural product. The excellent in vivo activity and improved water solubility of phosphate analogues 3m and 4g suggest their use as potential pro-drugs.

  合成了几种半合成的双-和单-O-烷基Nocathiacin衍生物，并评估了其抗菌活性。通过区域选择性烷基化制备单-O-烷基N-羟基吲哚类似物3a-1。通过用碱和过量的亲电试剂处理，获得双-O-烷基Nocathiacins 4a-f。为了制备单-O-烷基羟基吡啶类似物5a，b，开发了一种一锅保护-烷基化-脱保护策略。与天然产物相比，大多数的双-和单-O-烷基Nocathiacins保持良好的体外活性，但显示出降低的体内功效。磷酸盐类似物3m和4g的出色的体内活性和改善的水溶性表明它们可用作潜在的前药。
• Organic reactions in frozen water: Michael addition of amines and thiols to the dehydroalanine side chain of nocathiacins
  作者：B.Narasimhulu Naidu、Wenying Li、Margaret E. Sorenson、Timothy P. Connolly、John A. Wichtowski、Yunhui Zhang、Oak K. Kim、John D. Matiskella、Kin S. Lam、Joanne J. Bronson、Yasutsugu Ueda

  DOI：10.1016/j.tetlet.2003.11.081

  日期：2004.1

  In order to overcome this problem, we developed unique conditions in which Michael addition of amine and thiol nucleophiles to the dehydroalanine moiety of nocathiacins was successfully achieved in frozen water. Under these conditions, the Michael addition was highly chemoselective, very efficient and provided good isolated yields of the desired products.

  Nocathiacins是密集功能化的环状噻唑基肽天然产物，对多种革兰氏阳性细菌（包括多种多重耐药菌株）具有强大的体外和体内抗菌活性。尝试在已知条件下制备迈克尔加合物导致形成复杂的产物混合物。为了克服这个问题，我们开发了独特的条件，其中在冷冻水中成功地实现了将胺和巯基亲核试剂的迈克尔加成到Nocathiacins的脱氢丙氨酸部分中。在这些条件下，迈克尔加成物具有高度的化学选择性，非常有效，并提供了所需产物的良好分离产率。
• Synthesis and antibacterial activity of O-substituted nocathiacin I derivatives
  作者：B.Narasimhulu Naidu、Margaret E Sorenson、Thomas Hudyma、Xiaofan Zheng、Yunhui Zhang、Joanne J Bronson、Michael J Pucci、Junius M Clark、Yasutsugu Ueda

  DOI：10.1016/j.bmcl.2004.04.102

  日期：2004.7

  The synthesis and antibacterial activity of a series of new nocathiacin I derivatives (1-12) containing polar water solubilizing groups is described. Most of these compounds exhibited potent antibacterial activity and have improved water solubility. In addition, compounds 5, 7-9 also exhibited potent in vivo activity.

  描述了一系列含有极性水溶性基团的新型Nocathiacin I衍生物（1-12）的合成和抗菌活性。这些化合物大多数显示出有效的抗菌活性，并具有改善的水溶性。另外，化合物5、7-9也表现出有效的体内活性。
• Nocathiacin I analogues: synthesis, in vitro and in vivo biological activity of novel semi-synthetic thiazolyl peptide antibiotics
  作者：B. Narasimhulu Naidu、Margaret E. Sorenson、Yunhui Zhang、Oak K. Kim、John D. Matiskella、John A. Wichtowski、Timothy P. Connolly、Wenying Li、Kin S. Lam、Joanne J. Bronson、Michael J. Pucci、Junius M. Clark、Yasutsugu Ueda

  DOI：10.1016/j.bmcl.2004.08.058

  日期：2004.11

  Several nocathiacin I analogues (4-35) were synthesized and evaluated for their antibacterial activity. Most of these semi-synthetic analogues retained very good in vitro and in vivo antibacterial activity of 1.

  合成了几种Nocathiacin I类似物（4-35）并评估了其抗菌活性。这些半合成类似物中的大多数在体外和体内的抗菌活性均保持为1。
• WO2007/127136
  申请人：——

  公开号：——

  公开（公告）日：——