(S)-2-Amino-3-hydroxy-propionic acid dodecyl ester | 114119-20-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-Amino-3-hydroxy-propionic acid dodecyl ester
• 英文别名: dodecyl L-serinate；dodecyl (2S)-2-amino-3-hydroxypropanoate
• CAS: 114119-20-9
• 化学式: C₁₅H₃₁NO₃
• 分子量: 273.416
• InChiKey: ALECQBSCXXODGP-AWEZNQCLSA-N

物化性质

• 沸点：
  396.9±22.0 °C(Predicted)
• 密度：
  0.972±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-Amino-3-hydroxy-propionic acid dodecyl ester 在 potassium permanganate 、 DH-18-C-6 、 TEA 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.5h， 生成
  参考文献：
  名称：

  l-Serine and glycine based ceramide analogues as transdermal permeation enhancers: polar head size and hydrogen bonding

  摘要：

  Novel transdermal permeation enhancers related to stratum corneum ceramides were investigated. The synthesis of a series of simple compounds based on two selected amino acids, L-serine and glycine, and their enhancement activities are reported. Glycine derivative 3 enhanced the permeation of theophylline through human skin in vitro 12.5 +/- 0.5 times. The relationships between properties of the polar head of the compounds and their activity are discussed. (C) 2003 Elsevier Science Ltd. Ail rights reserved.

  DOI：

  10.1016/s0960-894x(03)00409-8
• 作为产物：
  描述：

  L-丝氨酸 、 十二烷醇 在 对甲苯磺酰肼 作用下， 以 甲苯 为溶剂， 以2.5 g的产率得到(S)-2-Amino-3-hydroxy-propionic acid dodecyl ester
  参考文献：
  名称：

  Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect

  摘要：

  Serine palmitoyltransferase (SPT) plays the key role on catalysing the formation of 3-ketodihydrosphingosine, which is the first step of the de novo biosynthesis of sphingolipids. SPT is linked to many diseases including fungal infection, making it a potential therapeutic target. Thus, a logical docking-based virtual screening method was used to screen selective SPT inhibitor against fungi, not human. We used myriocin-similarity database to identify compounds with good binding with fungal SPT and poor binding with homology human SPT model. Preliminary bio-assay led to the discovery of a promising inhibitor WXP-003, which displayed good inhibitory activity against diversity fungi strains with MIC ranging from 0.78 to 12.5 μg/mL. WXP-003 could significantly reduce sphingolipids content in fungi and no effect on mouse fibroblast cell line L929. Molecular dynamics simulation depicted that SPT/WXP-003 complex formed the favoured interactions. Taken together, discovery of WXP-003 provided valuable guide for the development of novel anti-fungal agents.

  DOI：

  10.1080/14756366.2021.1915301

文献信息

• [EN] TRANSDERMAL PENETRATION ENHANCERS<br/>[FR] ACTIVATEURS DE PENETRATION TRANSDERMIQUE
  申请人：UNIV KARLOVA

  公开号：WO2004074235A1

  公开（公告）日：2004-09-02

  The invention provides compounds based on ceramide analogues of the general the general formula (I), wherein R1= H or CH2OH; R2 = C8 to C16 alkyl; R3 = C7 to C15 alkyl, cis-heptadec-8­-en-1-yl, CH(R1)NHCOR4, CH=CHCOOR4 or CH(OH)CH(OH)COOR4; R4 = C7 to C16 alkyl. The compounds of the general formula (I) are used as transdermal penetration enhancers. Pharmaceutical and cosmetic compositions, containing ceramide analogues of the general formula (I) in the amount from 0.1 to 5.0 w/w percent, preferably in the amount from 0.1 to 1.0 w/w percent.

  该发明提供了一种基于泛用式(I)的神经酰胺类似物的化合物，其中R1= H或CH2OH；R2 = C8到C16烷基；R3 = C7到C15烷基、顺式-庚十七烯-8-基、CH(R1)NHCOR4、CH=CHCOOR4或CH(OH)CH(OH)COOR4；R4 = C7到C16烷基。泛用式(I)的化合物被用作经皮渗透增强剂。含有泛用式(I)的神经酰胺类似物的药用和化妆品组合物，其含量从0.1%到5.0%重量/重量百分比，最好在0.1%到1.0%重量/重量百分比。
• Synthetic ceramide analogues as skin permeation enhancers: structure–Activity relationships
  作者：Kateřina Vávrová、Alexandr Hrabálek、Pavel Doležal、Lucie Šámalová、Karel Palát、Jarmila Zbytovská、Tomáš Holas、Jana Klimentová

  DOI：10.1016/j.bmc.2003.09.034

  日期：2003.12

  The study presents new information about the structure-activity relationships of the skin permeation enhancers. A series of ceramide analogues including eight different polar head groups and six different chain lengths was synthesised. The compounds were evaluated as permeation enhancers in vitro using porcine skin. The physico-chemical parameters of the tested compounds obtained by computer modelling were used to evaluate, by multiple linear regression, the enhancement ratios (ERs) of the compounds. The regression analysis suggests that the hydrogen bonding ability of the compounds is inversely related to the ER values and that the molecular size and lipophilicity must be well balanced. In the studied enhancers having the same chain length, the enhancement activity is dependent only on their permeability coefficients. This finding confirms the Warner's hypothesis that the polar head of an enhancer is responsible for the permeation and anchoring of the molecule into the stratum corneum lipids and that it does not influence the mechanism of action. For the specific action of enhancers, that is disordering of the intercellular lipid packing, the length of the hydrophobic chain(s) and not the lipophilicity is important. Furthermore, the examination of the FTIR spectra indicated that the most active substances possess the most ordered chains. The described relationships could bring more rational approaches in designing new potent enhancers for transdermal formulations. (C) 2003 Elsevier Ltd. All rights reserved.
• l-Serine and glycine based ceramide analogues as transdermal permeation enhancers: polar head size and hydrogen bonding
  作者：Kateřina Vávrová、Alexandr Hrabálek、Pavel Doležal、Tomáš Holas、Jarmila Zbytovská

  DOI：10.1016/s0960-894x(03)00409-8

  日期：2003.7

  Novel transdermal permeation enhancers related to stratum corneum ceramides were investigated. The synthesis of a series of simple compounds based on two selected amino acids, L-serine and glycine, and their enhancement activities are reported. Glycine derivative 3 enhanced the permeation of theophylline through human skin in vitro 12.5 +/- 0.5 times. The relationships between properties of the polar head of the compounds and their activity are discussed. (C) 2003 Elsevier Science Ltd. Ail rights reserved.
• Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect
  作者：Xin Wang、Xin Yang、Xin Sun、Yi Qian、Mengyao Fan、Zhehao Zhang、Kaiyuan Deng、Zaixiang Lou、Zejun Pei、Jingyu Zhu

  DOI：10.1080/14756366.2021.1915301

  日期：2021.1.1

  Serine palmitoyltransferase (SPT) plays the key role on catalysing the formation of 3-ketodihydrosphingosine, which is the first step of the de novo biosynthesis of sphingolipids. SPT is linked to many diseases including fungal infection, making it a potential therapeutic target. Thus, a logical docking-based virtual screening method was used to screen selective SPT inhibitor against fungi, not human. We used myriocin-similarity database to identify compounds with good binding with fungal SPT and poor binding with homology human SPT model. Preliminary bio-assay led to the discovery of a promising inhibitor WXP-003, which displayed good inhibitory activity against diversity fungi strains with MIC ranging from 0.78 to 12.5 μg/mL. WXP-003 could significantly reduce sphingolipids content in fungi and no effect on mouse fibroblast cell line L929. Molecular dynamics simulation depicted that SPT/WXP-003 complex formed the favoured interactions. Taken together, discovery of WXP-003 provided valuable guide for the development of novel anti-fungal agents.