苯甲醇,-α--甲基-4-(2-甲基丙基)-,乙酸酯(9CI) | 139149-55-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 中文名称: 苯甲醇,-α--甲基-4-(2-甲基丙基)-,乙酸酯(9CI)
• 英文名称: (S)-(+)-N-(6-benzyloxy-2,3-dihydrobenzofuran-3-yl)-N-hydroxyurea
• 英文别名: SB 202235；(S) N-[6-Benzyloxy-2,3-dihydrobenzofuran-3-yl]hydroxyurea；(S)-N-[6-Benzyloxy-2,3-dihydrobenzofuran-3-yl]hydroxyurea；(S)-(+)-N-hydroxy-N-[2,3-dihydro-6-(benzyloxy)benzofuran-3-yl]urea；N-((3S)-2,3-Dihydro-6-(phenylmethoxy)-3-benzofuranyl)-N-hydroxyurea；1-hydroxy-1-[(3S)-6-phenylmethoxy-2,3-dihydro-1-benzofuran-3-yl]urea
• CAS: 139149-55-6
• 化学式: C₁₆H₁₆N₂O₄
• 分子量: 300.314
• InChiKey: FYAQEFBDKOWIIL-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  85
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-苯甲氧基-2-羟基苯甲醛 在 三正丁胺 、 盐酸羟胺 、 碳酸氢钠 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 6.0h， 生成 苯甲醇,-α--甲基-4-(2-甲基丙基)-,乙酸酯(9CI)
  参考文献：
  名称：

  对映体选择性合成抑制5-LO的羟基脲。串联亲核加成和分子内环化法构建二氢-苯并呋喃核

  摘要：

  基于将二甲基亚砜基叶立德亲核加成到带有甘露糖衍生的手性助剂的腈上，描述了对5-LO抑制性手性羟基脲的对映选择性合成。然后通过初始加合物的自发环化来构建二氢苯并呋喃骨架，从而完成串联亲核加成-环化方案。

  DOI：

  10.1016/0040-4039(96)00922-7

文献信息

• Synthesis of acid addition salts of hydroxylamines
  申请人：Smithkline Beecham Corporation

  公开号：US05663368A1

  公开（公告）日：1997-09-02

  This invention relates to novel diastereomeric acid addition salts of homochiral hydroxylamines, to processes for obtaining such, to processes for the conversion thereof to the corresponding homochiral hydroxylamines, to certain novel homochiral hydroxylamines and the processes for using these as intermediates.

  该发明涉及新型异构酸加成盐，这些盐是同手性羟胺的盐，涉及获得这种盐的方法，将其转化为相应的同手性羟胺的方法，特定的新型同手性羟胺以及使用这些同手性羟胺作为中间体的方法。
• Asymmetric synthesis of N-substituted N-hydroxyureas
  作者：Krzysztof Z. Łączkowski、Marcin M. Pakulski、Marek P. Krzemiński、Parasuraman Jaisankar、Marek Zaidlewicz

  DOI：10.1016/j.tetasy.2008.03.008

  日期：2008.4

  Asymmetric synthesis of (S)-N-(1-arylethyl)-N-hydroxyureas, (S)-N-(6-methoxy)- and (S)-N-(6-benzyloxy-2,3-dihydrobenzofuran-3-yl)-N-hydroxyurea— lipoxygenase inhibitor, is described. Three approaches to the formation of the N-hydroxyurea moiety at the stereogenic center have been used. The first one, via the reaction of (R)-6-benzyloxy-2,3-dihydrobenzofuran-3-ol with N,O-bis(phenoxycarbonyl)hydroxylamine

  （S）-N-（1-芳基乙基）-N-羟基脲，（S）-N-（6-甲氧基）-和（S）-N-（6-苄氧基-2,3-二氢苯并呋喃-3 ）的不对称合成描述了（β-基）-N-羟基脲-脂氧合酶抑制剂。已经使用了三种在立体发生中心形成N-羟基脲部分的方法。第一种，通过（R）-6-苄氧基-2，3-二氢苯并呋喃-3-醇与N，O-双（苯氧基羰基）羟胺在Mitsunobu条件下反应，得到部分消旋的产物。或者，肟的对映选择性还原可以控制苯乙酮，4-甲氧基-和4-苄氧基苯乙酮，6-甲氧基-和6-苄氧基-2,3-二氢苯并呋喃-3-酮与硼烷/恶唑硼烷的O-苄基醚生成相应的羟胺O-苄基醚或伯胺，它们已以57％到99％ee转化为N-取代的N-羟基脲。
• Bicyclic N-Hydroxyurea Inhibitors of 5-Lipoxygenase:  Pharmacodynamic, Pharmacokinetic, and <i>in Vitro</i> Metabolic Studies Characterizing <i>N</i>-Hydroxy-<i>N</i>-(2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl)urea
  作者：Jerry L. Adams、Ravi S. Garigipati、Margaret Sorenson、Stanley J. Schmidt、William R. Brian、John F. Newton、Kathy A. Tyrrell、Eric Garver、Lee A. Yodis、Marie Chabot-Fletcher、Maritsa Tzimas、Edward F. Webb、John J. Breton、Don E. Griswold

  DOI：10.1021/jm960271d

  日期：1996.1.1

  A series of N-hydroxyurea derivatives have been prepared and examined as inhibitors of 5-lipoxygenase. Oral activity was established by examining the inhibition of LTB(4) biosynthesis in an ex vivo assay in the mouse. The pharmacodynamic performance in the mouse of selected compounds was assessed using an ex vivo LTB(4) assay and an adoptive peritoneal anaphylaxis assay at extended pretreat times. Compounds with an extended duration of action were reexamined as the individual enantiomers in the ex vivo assay, and the (S) enantiomer of N-hydroxy-N-[2,3-dihydro-6-(phenylmethoxy)-3-benzofuranyl]urea, (+)-1a (SE 202235), was selected as the compound with the best overall profile. Higher plasma concentrations and longer plasma half-lives were found for (+)-1a relative to its enantiomer in the mouse, monkey, and dog. In vitro metabolic studies in mouse liver microsomes established enantiospecific glucuronidation as a likely mechanism for the observed differences between the enantiomers of la. Enantioselective glucuronidation favoring (-)-1a was also found in human liver microsomes.
• Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones
  作者：Ivan Lantos、Joseph Flisak、Li Liu、Richard Matsuoka、Wilf Mendelson、David Stevenson、Ken Tubman、Lynn Tucker、Wei-Yuan Zhang、Jerry Adams、Margaret Sorenson、Ravi Garigipati、Karl Erhardt、Steve Ross

  DOI：10.1021/jo9621736

  日期：1997.8.1

  An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.
• Resolution of hydroxyureas
  作者：Ravi S. Garigipati、Margaret E. Sorenson、Karl F. Erhard、Jerry L. Adams

  DOI：10.1016/s0040-4039(00)73875-5

  日期：1993.8

  Racemic hydroxyureas can be efficiently resolved on a preparative scale using (4S)-4-benzyl-2-oxazolidinone-3-carbonyl chloride 3. The resulting carbamates can be separated by chromatography and hydrolysis of these diastereomers yields enantiomerically pure hydroxyureas.