N-((2S,4R)-1,4-dihydroxy-4-phenylbutan-2-yl)dodecanamide | 475293-70-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-((2S,4R)-1,4-dihydroxy-4-phenylbutan-2-yl)dodecanamide
• 英文别名: N-[(2S,4R)-1,4-dihydroxy-4-phenylbutan-2-yl]dodecanamide
• CAS: 475293-70-0
• 化学式: C₂₂H₃₇NO₃
• 分子量: 363.541
• InChiKey: YCAKBKAOFSILDC-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯乙烯 在 4-二甲氨基吡啶 、 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 、 盐酸羟胺 、 水 、 potassium carbonate 、 对甲苯磺酸 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 69.5h， 生成 N-((2S,4R)-1,4-dihydroxy-4-phenylbutan-2-yl)dodecanamide
  参考文献：
  名称：

  通过Ru催化的异恶唑烷的N-脱甲基重排合成合成-1,3-氨基醇及其在HPA-12的三步全合成中的应用

  摘要：

  描述了异恶唑烷对合成有用的N –H-1,3-恶二嗪酮的高效钌催化的立体特异性N-脱甲基重排。1,3- Oxazinanes是有用的构建块，其可以被进一步转化为Ñ -H -1,3-氨基醇在一个步骤。这项新方法用于HPA-12的三步克级总合成中，总产率为24％。

  DOI：

  10.1021/ol502956j

文献信息

• Revised Stereochemistry of Ceramide-Trafficking Inhibitor HPA-12 by X-ray Crystallography Analysis
  作者：Masaharu Ueno、Yi-Yong Huang、Akihito Yamano、Shu̅ Kobayashi

  DOI：10.1021/ol401101u

  日期：2013.6.7

  the stereochemistry of HPA-12, an important ceramide-trafficking inhibitor that was discovered and synthesized and its stereochemistry determined in 2001, the synthesis and the stereochemistry were reinvestigated. A large-scale synthetic method for HPA-12 based on a Zn-catalyzed asymmetric Mannich-type reaction in water was developed. Single crystals of HPA-12 for X-ray crystallographic analysis were

  响应伯克什（Berkeš）的报告，修改和合成了重要的神经酰胺贩运抑制剂HPA-12的立体化学，并于2001年确定了其立体化学，对此合成和立体化学进行了重新研究。提出了一种基于锌催化水中不对称曼尼希型反应的HPA-12大规模合成方法。由丙酸乙酯/获得用于X射线晶体学分析HPA-12的单晶Ñ己烷，和立体化学明确确定为1 - [R，3小号，与贝尔克斯订正结构一致。
• A domino Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines and application to the synthesis of the ceramide transport inhibitor (±)-HPA-12
  作者：Sarah V.A.-M. Legendre、Martyn Jevric、Julian Klepp、Christopher J. Sumby、Ben W. Greatrex

  DOI：10.1016/j.tet.2017.11.010

  日期：2018.3

  A Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines with primary and secondary amines has been developed which affords 4-hydroxy-3-aminoketones. The aza-Michael products were reduced using non-selective NaBH4/MeOH or diastereoselective (up to 92:8) SnCl4/NaBH4 conditions yielding (1R*,3S*)-3-amino-1,4-diols in up to 97% and 70% yield respectively. The major reduction product was converted in two steps to (+/-)-HPA-12, which is an inhibitor of the cytosolic ceramide transporting protein. (C) 2017 Elsevier Ltd. All rights reserved.
• Ruthenium-Catalyzed Asymmetric <i>N</i>-Demethylative Rearrangement of Isoxazolidines and Its Application in the Asymmetric Total Syntheses of (−)-(1<i>R</i>,3<i>S</i>)-HPA-12 and (+)-(1<i>S</i>,3<i>R</i>)-HPA-12
  作者：Zu-Feng Xiao、Chuan-Zhi Yao、Yan-Biao Kang

  DOI：10.1021/ol503261h

  日期：2014.12.19

  An asymmetric N-demethylative rearrangement of 1,2-isoxazolidines catalyzed by ruthenium is described. Enantioenriched syn-1,3-aminoalcohols as well as cis-1,3-oxazinanes, which are useful building blocks, can be efficiently prepared stereospecifically by this reaction in good yields, via the isoxazolidine intermediates in situ generated from a nitrone bearing a chiral auxiliary and styrenes. This asymmetric reaction was also applied in the asymmetric total syntheses of both (-)-(1R,3S)-HPA-12 and (+)-(1S,3R)-HPA-12.
• BF₃-Mediated <i>cis</i>-Selective Cycloaddition of <i>O</i>-Silyloxime with Alkenes
  作者：Nobuyoshi Morita、Rina Kono、Kenji Fukui、Asuka Miyazawa、Hyuma Masu、Isao Azumaya、Shintaro Ban、Yoshimitsu Hashimoto、Iwao Okamoto、Osamu Tamura

  DOI：10.1021/acs.joc.5b00426

  日期：2015.5.1

  A C-amide-substituted O-silylated oxime, (E)-(tert-butyldimethylsiloxyimino)acetic acid N,N-dimethylamide (8b), on treatment with 2.2 equiv of BF3 center dot OEt2, in situ generated boracyclic nitrone-type intermediate BF3 center dot 14, which underwent cycloaddition with alkenes to give 3,5-cis-isoxazolidines as the Major products. The mechanism was strongly supported by isolation of the reaction intermediate 14 that was characterized by X-ray diffraction and its further reaction. This cycloaddition was successfully applied to the synthesis of syn-HPA-12 known as an inhibitor of CERT that mediates the transport of ceramide.