(1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide | 384835-42-1

• 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: (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
• 英文别名: HPA-12；(1R,3R)-HPA-12；N-[(2R,4R)-1,4-dihydroxy-4-phenylbutan-2-yl]dodecanamide
• CAS: 384835-42-1
• 化学式: C₂₂H₃₇NO₃
• 分子量: 363.541
• InChiKey: YCAKBKAOFSILDC-NHCUHLMSSA-N

物化性质

• 熔点：
  90-91 °C
• 沸点：
  570.2±50.0 °C(Predicted)
• 密度：
  1.022±0.06 g/cm3(Predicted)

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

• 作为反应物：
  描述：

  (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 [(2R,4R)-1,4-dihydroxy-4-phenylbutan-2-yl]azanium;chloride
  参考文献：
  名称：

  Stereoselective Synthesis and Structure−Activity Relationship of Novel Ceramide Trafficking Inhibitors. (1R,3R)-N-(3-Hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide and Its Analogues

  摘要：

  New ceramide trafficking inhibitors, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12) and a series of its analogues, were synthesized in diastereomerically and enantiomerically pure forms, and the structure-activity relationship was investigated. These analogues were stereoselectively synthesized via catalytic enantioselective Mannich-type reactions using a Cu(II)-chiral diamine 4 complex. Analysis of HPA-12 analogues having various lengths of the amide side chain showed that the optimal chain length for the inhibition of sphingomyelin biosynthesis is 13 with an IC50 of similar to50 nM. Masking of the hydroxy group at the 2'- or 3-position of HPA-12 was carried out by methylation, and it was revealed that these hydroxy groups were essential for the activity. Installation of another hydroxy group onto HPA-12 at the same position as that in the natural ceramide was also conducted, but no enhancement of the activity was observed.

  DOI：

  10.1021/jm0300779
• 作为产物：
  描述：

  苯磺酰胺,4-甲基-N-(3-苯基-2-亚丙烯基)-,(E,E)- 在 吡啶 、 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 水 、 三正丁基氢锡 、 sodium naphthalenide 、 potassium carbonate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 氯仿 、 水 、 甲苯 、 乙腈 、 苯 为溶剂， 反应 37.52h， 生成 (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
  参考文献：
  名称：

  由β-对甲苯磺酰胺基-γ，δ-不饱和亚砜立体选择性合成（-）-烯丙二胺和（1 R，3 R）-HPA-12

  摘要：

  公开了（-）-烯丙二胺和HPA-12的立体选择性合成。合成的关键步骤包括β-磺酰胺基不饱和亚砜的非对映选择性合成，通过分子内亚磺酰基基团参与的溴代醇的精制以及用于构建异同胺的哌啶环的闭环易位反应。

  DOI：

  10.1016/j.tet.2004.04.019

文献信息

• Synthesis of β-Amino Ketones by Addition of Aryl Methyl Ketones to Sulfinimines: Application to the Total Synthesis of HPA-12, Norsedamine, and Sedamine
  作者：Arava Amaranadha Reddy、Kavirayani R. Prasad

  DOI：10.1021/acs.joc.7b02611

  日期：2017.12.15

  Synthesis of β-sulfinamido ketones was accomplished by the addition of silyl enol ethers derived from arylmethyl ketones to chiral sulfinimines in excellent yield and selectivity. Application of the formed β-amino substituted ketones is exemplified in the total synthesis of sphingolipid HPA-12 and the sedamine alkaloids.

  β-亚磺酰胺基酮的合成是通过将衍生自芳基甲基酮的甲硅烷基烯醇醚以优异的收率和选择性加入到手性亚磺胺中来完成的。形成的β-氨基取代的酮的应用在鞘脂类HPA-12和sedamine生物碱的全合成中得到了举例说明。
• Catalytic, Asymmetric Mannich-type Reactions of <i>N</i>-Acylimino Esters:  Reactivity, Diastereo- and Enantioselectivity, and Application to Synthesis of N-Acylated Amino Acid Derivatives
  作者：Shū Kobayashi、Ryosuke Matsubara、Yoshitaka Nakamura、Hidetoshi Kitagawa、Masaharu Sugiura

  DOI：10.1021/ja0281840

  日期：2003.3.1

  the synthesis of biologically important compounds were prepared using this novel catalytic asymmetric Mannich-type reaction, and at the same time, absolute and relative stereochemical assignments were made. In addition, it has been revealed that alkyl vinyl ethers reacted with N-acylimino esters in the presence of a catalytic amount of the Cu(II) catalyst to give the corresponding Mannich-type adducts

  在催化量的 Cu(OTf)(2)-手性二胺 3e 复合物存在下，N-酰基亚氨基酯与甲硅烷基烯醇醚反应以高产率和高对映选择性提供相应的曼尼希型加合物。各种衍生自酮的甲硅烷基烯醇醚以及酯和硫酯都能顺利反应。在α-取代的甲硅烷基烯醇醚（α-甲基或苄氧基）的反应中，以高产率和高非对映选择性和对映选择性获得了所需的顺式加合物。使用这种新型催化不对称曼尼希型反应制备了几种用于合成生物学上重要化合物的中间体，同时进行了绝对和相对立体化学分配。此外，已经表明，在催化量的 Cu(II) 催化剂存在下，烷基乙烯基醚与 N-酰基亚氨基酯反应，以高产率和高对映选择性得到相应的曼尼希型加合物。这是与烷基乙烯基醚催化不对称曼尼希型反应的第一个例子。基于Cu(II)-手性胺配合物的X射线晶体学分析、PM3计算和FT-IR分析等假设了反应机理、手性催化剂-亲电子配合物的结构以及这些催化不对称反应的过渡态. 最后，(1R,
• 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。
• The Catalytic Asymmetric Mannich-Type Reactions in Aqueous Media
  作者：Shū Kobayashi、Tomoaki Hamada、Kei Manabe

  DOI：10.1021/ja026094p

  日期：2002.5.1

  The catalytic, diastereo- and enantioselective Mannich-type reaction of a hydrazono ester with silyl enol ethers in aqueous media has been successfully achieved with ZnF(2), a chiral diamine ligand, and trifluoromethanesulfonic acid.

  用 ZnF(2)、手性二胺配体和三氟甲磺酸在水性介质中成功地实现了腙酯与甲硅烷基烯醇醚的催化、非对映选择性和对映选择性曼尼希型反应。
• Expedient and Practical Synthesis of CERT-Dependent Ceramide Trafficking Inhibitor HPA-12 and Its Analogues
  作者：Andrej Ďuriš、Tomáš Wiesenganger、Daniela Moravčíková、Peter Baran、Jozef Kožíšek、Adam Daïch、Dušan Berkeš

  DOI：10.1021/ol2001057

  日期：2011.4.1

  The practical stereodivergent route to both syn- and anti-diastereomers of 1-substituted 3-aminobutane-1,4-diols based on the crystallization-induced asymmetric transformation (CIAT) approach was completed. This led to the revision of the reported stereochemistry of the first inhibitor of CERT-dependent ceramide trafficking HPA-12 from (R,R)-anti- to the (R,S)-syn-enantiomer. Due to the expeditiousness of production and inexpensive conditions developed, a series of alkyl- and aryl-substituted analogues of HPA-12 is also reported.