(E)-1-(4-chlorophenyl)-2-(5-(hydroxymethyl)-1H-imidazol-1-yl)-4,4-dimethylpent-1-en-3-ol | 1192843-13-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-1-(4-chlorophenyl)-2-(5-(hydroxymethyl)-1H-imidazol-1-yl)-4,4-dimethylpent-1-en-3-ol
• 英文别名: DSI-501
• CAS: 1192843-13-2
• 化学式: C₁₇H₂₁ClN₂O₂
• 分子量: 320.819
• InChiKey: ZFFHRMXVQGBURY-OVCLIPMQSA-N

反应信息

• 作为反应物：
  描述：

  (E)-1-(4-chlorophenyl)-2-(5-(hydroxymethyl)-1H-imidazol-1-yl)-4,4-dimethylpent-1-en-3-ol 在 zinc(II) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 31.0h， 以27%的产率得到(E)-6-tert-butyl-5-(4-chlorobenzylidene)-6,8-dihydro-5H-imidazo[5,1-c][1,4]oxazine
  参考文献：
  名称：

  Abscinazole-F1, a conformationally restricted analogue of the plant growth retardant uniconazole and an inhibitor of ABA 8′-hydroxylase CYP707A with no growth-retardant effect

  摘要：

  To develop a specific inhibitor of abscisic acid (ABA) 8'-hydroxylase, a key enzyme in the catabolism of ABA, a plant hormone involved in stress tolerance, seed dormancy, and other various physiological events, we designed and synthesized conformationally restricted analogues of uniconazole (UNI), a well-known plant growth retardant, which inhibits a biosynthetic enzyme (ent-kaurene oxidase) of gibberellin as well as ABA 8'-hydroxylase. Although most of these analogues were less effective than UNI in inhibition of ABA 8'-hydroxylase and rice seedling growth, we found that a lactol-bridged analogue with an imidazole is a potent inhibitor of ABA 8'-hydroxylase but not of plant growth. This compound, abscinazole-F1, induced drought tolerance in apple seedlings upon spray treatment with a 10 mu M solution. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.070
• 作为产物：
  描述：

  (E)-2-(5-((tert-butyldimethylsilyloxy)methyl)-1H-imidazol-1-yl)-1-(4-chlorophenyl)-4,4-dimethylpent-1-en-3-ol 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 以89%的产率得到(E)-1-(4-chlorophenyl)-2-(5-(hydroxymethyl)-1H-imidazol-1-yl)-4,4-dimethylpent-1-en-3-ol
  参考文献：
  名称：

  Abscinazole-F1, a conformationally restricted analogue of the plant growth retardant uniconazole and an inhibitor of ABA 8′-hydroxylase CYP707A with no growth-retardant effect

  摘要：

  To develop a specific inhibitor of abscisic acid (ABA) 8'-hydroxylase, a key enzyme in the catabolism of ABA, a plant hormone involved in stress tolerance, seed dormancy, and other various physiological events, we designed and synthesized conformationally restricted analogues of uniconazole (UNI), a well-known plant growth retardant, which inhibits a biosynthetic enzyme (ent-kaurene oxidase) of gibberellin as well as ABA 8'-hydroxylase. Although most of these analogues were less effective than UNI in inhibition of ABA 8'-hydroxylase and rice seedling growth, we found that a lactol-bridged analogue with an imidazole is a potent inhibitor of ABA 8'-hydroxylase but not of plant growth. This compound, abscinazole-F1, induced drought tolerance in apple seedlings upon spray treatment with a 10 mu M solution. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.070

文献信息

• Selectivity improvement of an azole inhibitor of CYP707A by replacing the monosubstituted azole with a disubstituted azole
  作者：Yasushi Todoroki、Kumi Naiki、Hikaru Aoyama、Minaho Shirakura、Kotomi Ueno、Masaharu Mizutani、Nobuhiro Hirai

  DOI：10.1016/j.bmcl.2010.07.067

  日期：2010.9

  The plant growth-retardant uniconazole (UNI), a triazole inhibitor of gibberellin biosynthetic enzyme (CYP701A), inhibits multiple P450 enzymes including ABA 8'-hydroxylase (CYP707A), a key enzyme in ABA catabolism. Azole P450 inhibitors bind to a P450 active site by both coordinating to the heme-iron atom via sp(2) nitrogen and interacting with surrounding protein residues through a lipophilic region. We hypothesized that poor selectivity of UNI may result from adopting a distinct conformation and orientation for different active sites. Based on this hypothesis, we designed and synthesized novel UNI analogs with a disubstituted azole ring (DSI). These analogs were expected to have higher selectivity than UNI because the added functional group may interact with the active site to restrict orientation of the molecule in the active site. DSI-505ME and DSI-505MZ, which have an imidazolyl group with a methyl 5-acrylate, strongly inhibited recombinant CYP707A3, with no growth-retardant effect. (C) 2010 Elsevier Ltd. All rights reserved.