(5S)-3-bromo-5-hydroxymethyl-Δ²-isoxazoline | 128993-17-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: (5S)-3-bromo-5-hydroxymethyl-Δ²-isoxazoline
• 英文别名: (S)-(3-bromo-4,5-dihydroisoxazol-5-yl)methanol；(5S)-3-Bromo-4,5-dihydro-5-isoxazolemethanol；[(5S)-3-bromo-4,5-dihydro-1,2-oxazol-5-yl]methanol
• CAS: 128993-17-9
• 化学式: C₄H₆BrNO₂
• 分子量: 180.001
• InChiKey: WHYBJMZOIKMVCQ-VKHMYHEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5S)-3-bromo-5-hydroxymethyl-Δ²-isoxazoline 在 甲基磺酰氯 、 三乙胺 、 sodium azide 、 二甲基亚砜 、 三苯基膦 作用下， 以 二氯甲烷 、 四氢呋喃 、 水 为溶剂， 反应 44.0h， 以94%的产率得到
  参考文献：
  名称：

  新型拟肽类药物作为罗丹素抑制剂的合成及生物学评价。

  摘要：

  通过将对映体纯的3-溴异恶唑啉战斗部与作为特定识别部分的1,4-苯并二氮杂sc骨架相结合，开发出了新型罗得沙因抑制剂。事实证明，所有化合物均能抑制罗得沙因，其Ki值在低微摩尔范围内。发现它们对罗德沙因的活性与体外抗锥虫活性有关，IC50值范围从最活跃的罗德沙因抑制剂（R，S，S）-3的中微摩尔值到低微摩尔值。由于所有化合物均被证明是人组织蛋白酶L的弱抑制剂，因此所有化合物均对目标酶具有良好的选择性。

  DOI：

  10.3109/14756366.2015.1108972
• 作为产物：
  描述：

  ((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl acetate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以82%的产率得到(5S)-3-bromo-5-hydroxymethyl-Δ²-isoxazoline
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of the Selective Inhibition of Transglutaminase 2 by Dihydroisoxazoles

  摘要：

  Human transglutaminase 2 (TG2) is believed to play an important role in the pathogenesis of various human disorders including celiac sprue, certain neurological diseases, and some types of cancer. Selective inhibition of TG2 should therefore enable further investigation of its role in physiology and disease and may lead to effective clinical treatment. Recently we showed that certain 3-halo-4-,5-dihydroisoxazole containing compounds are selective inhibitors of human TG2 with promising pharmacological activities. Here, we present definitive evidence that this class of compounds targets the active site of human TG2. Structure-activity relationship studies have provided insights into the structural prerequisites for selectivity and have led to the discovery of an inhibitor with about 50-fold higher activity than a prototypical dihydroisoxazole inhibitor with good in vivo activity. A method for preparing enantiomerically enriched analogues was also developed. Our studies show that the 5-(S)-dihydroisoxazole is a markedly better inhibitor of human TG2 than its 5-(R) stereoisomer.

  DOI：

  10.1021/jm060839a

文献信息

• Nitrile oxides in medicinal chemistry. 5. Lipase PS-catalyzed resolution of a set of heterocyclic derivatives.
  作者：Giacomo Carrea、Marco de Amici、Carlo de Micheli、Paola Liverani、Marta Carnielli、Sergio Riva

  DOI：10.1016/s0957-4166(00)80155-x

  日期：1993.5

  Lipase from Pseudomonas cepacia (lipase PS) catalyzed the hydrolysis of a series of butyrates of racemic primary alcohols carrying a Δ2-isoxazoline or an isoxazolidin-3-one nucleus. Within this set of compounds, the enantiopreference of the catalyst can be accounted for by a rule recently proposed for lipase PS-catalyzed resolution of secondary alcohols. Nevertheless much work needs to be done in order

  从脂肪酶洋葱假单胞菌（脂肪酶PS）催化的一系列承载Δ外消旋伯醇丁酸酯的水解2 -isoxazoline或异恶唑烷-3-酮核。在这组化合物中，催化剂的对映体优先性可通过最近提出的关于脂肪酶PS催化仲醇拆分的规则来解释。然而，为了预测对映选择性的程度和相对反应速率，需要做很多工作。
• Development of Rhodesain Inhibitors with a 3-Bromoisoxazoline Warhead
  作者：Roberta Ettari、Lucia Tamborini、Ilenia C. Angelo、Silvana Grasso、Tanja Schirmeister、Leonardo Lo Presti、Carlo De Micheli、Andrea Pinto、Paola Conti

  DOI：10.1002/cmdc.201300390

  日期：2013.12

  Novel rhodesain inhibitors were obtained by combining an enantiomerically pure 3‐bromoisoxazoline warhead with a specific peptidomimetic recognition moiety. All derivatives behaved as inhibitors of rhodesain, with low micromolar Ki values. Their activity against the enzyme was found to be paralleled by an in vitro antitrypanosomal activity, with IC50 values in the mid‐micromolar range. Notably, a preference

  通过将对映体纯的3-溴异恶唑啉战斗部与特定的拟肽识别部分相结合，可获得新型的罗德萨因抑制剂。所有衍生物均表现为罗得沙星的抑制剂，其微摩尔K i值低。发现它们对酶的活性与体外抗锥虫活性平行，IC 50值在中微摩尔范围内。值得注意的是，观察到寄生虫优于人蛋白酶，特别是组织蛋白酶B和L。
• Nitrile oxides in medicinal chemistry-2. synthesis of the two enantiomers of dihydromuscimol
  作者：Marco De Amici、Carlo De Micheli、Valeria Misani

  DOI：10.1016/s0040-4020(01)89765-9

  日期：1990.1
• Nitrile oxides in medicinal chemistry. 4. Chemoenzymic synthesis of chiral heterocyclic derivatives
  作者：Marco De Amici、Paolo Magri、Carlo De Micheli、Francesca Cateni、Roberto Bovara、Giacomo Carrea、Sergio Riva、Gianluigi Casalone

  DOI：10.1021/jo00036a013

  日期：1992.5

  The two enantiomers of 3-bromo-5-(hydroxymethyl)-DELTA-2-isoxazoline (1) and 2-phenyl-5-(hydroxymethyl)-isoxazolidin-3-one (9) have been prepared in enantiomeric excess higher than 90% by hydrolysis of the corresponding butyrates under the catalysis of lipase PS, which was the most selective catalyst of the enzymes tested. The pairs of enantiomers of 1 and 9 were transformed into the chiral forms of the potent muscarinic ligands 3 and 5. The results obtained with the homogeneous set of esters 6, 7, 10a-d evidence a strong dependence of reaction rate and enantioselectivity of the lipase PS-catalyzed transformations upon both the size of the acyl moiety and the shape of the group carrying the alcoholic part of the ester. In the series of esters 10a-d, the best results were obtained with butyrate 10b. Quite interestingly, on passing from the butyrate of 1 to that of 9, the value of the enantiomeric ratio remained remarkably high but the enantiopreference switched from R to S. In between lies the butyrate of 2-methyl-5-(hydroxymethyl)isoxazolidin-3-one [(+/-)-6] which was barely recognized by lipase PS and yielded alcohol (R)-(-)-2 in a modest enantiomeric excess.
• Carnielli; De Amici; De Micheli, Il Farmaco, 1995, vol. 50, # 1, p. 21 - 27
  作者：Carnielli、De Amici、De Micheli、Gianferrara、Maurich、Zacchigna、Grana、Boselli

  DOI：——

  日期：——