N-((2S,3R,E)-1,3-dihydroxyoctadec-4-en-2-yl)-32-(linoleoyloxy)dotriacontanamide

• 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,3R,E)-1,3-dihydroxyoctadec-4-en-2-yl)-32-(linoleoyloxy)dotriacontanamide
• 英文别名: N-(omega-linoleoyloxydotricontanoyl)sphingosine；[32-[[(E,2S,3R)-1,3-dihydroxyoctadec-4-en-2-yl]amino]-32-oxodotriacontyl] (9Z,12Z)-octadeca-9,12-dienoate
• 化学式: C₆₈H₁₂₉NO₅
• 分子量: 1040.78
• InChiKey: NKZDGPMKCOVGRH-ARKMRHPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  27.3
• 重原子数：
  74
• 可旋转键数：
  63
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  16-溴-1-十六烷醇 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 草酰氯 、 2,4,6-三氯苯甲酰氯 、 palladium 10% on activated carbon 、 氢气 、 sodium hexamethyldisilazane 、 4-甲基苯磺酸吡啶 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 130.5h， 生成 N-((2S,3R,E)-1,3-dihydroxyoctadec-4-en-2-yl)-32-(linoleoyloxy)dotriacontanamide
  参考文献：
  名称：

  Scalable Synthesis of Human Ultralong Chain Ceramides

  摘要：

  Ceramides with ultralong chains (>30 carbons), also known as acylceramides, play a critical role in the survival of mammals on dry land. An efficient and scalable synthesis of four major classes of ultralong human skin ceramides is reported. The key approach involves the use of a succinimidyl ester that acts as a protective group, helps overcome the extremely low solubility, and simultaneously activates the fatty acid for its clean and high-yielding attachment to a sphingoid base.

  DOI：

  10.1021/acs.orglett.5b02816

文献信息

• PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis
  作者：Tetsuya Hirabayashi、Tatsuki Anjo、Arisa Kaneko、Yuuya Senoo、Akitaka Shibata、Hiroyuki Takama、Kohei Yokoyama、Yasumasa Nishito、Tomio Ono、Choji Taya、Kazuaki Muramatsu、Kiyoko Fukami、Agustí Muñoz-Garcia、Alan R. Brash、Kazutaka Ikeda、Makoto Arita、Masashi Akiyama、Makoto Murakami

  DOI：10.1038/ncomms14609

  日期：——

  Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation. In Pnpla1^−/− epidermis, unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-ω-hydroxy fatty acids are almost absent with reciprocal increases in their putative precursors, indicating that PNPLA1 catalyses the ω-O-esterification with linoleic acid to form acylceramides. Moreover, acylceramide supplementation partially rescues the altered differentiation of Pnpla1^−/− keratinocytes. Our findings provide valuable insight into the skin barrier formation and ichthyosis development, and may contribute to novel therapeutic strategies for treatment of epidermal barrier defects.

  位于马铃薯素磷脂酶结构域1（PNPLA1）的突变导致常染色体隐性遗传性先天性鱼鳞病，但涉及的机制尚不清楚。在这里，我们展示了PNPLA1是一种在分化的角质细胞中表达的酶，对于皮肤屏障必需的脂质成分ω-O-酰胺的生物合成起着至关重要的作用。全身或角质细胞特异性Pnpla1缺失的新生儿因表皮渗透屏障缺陷而死亡，伴有严重的经皮水分散失，角质层中间隔脂质减少和异常的角质细胞分化。在Pnpla1^−/−表皮中，独特的亚油酸含量的脂质，包括酰胺、酰基葡糖酰胺和（O-酰基）-ω-羟基脂肪酸几乎不存在，其潜在的前体物质相应增加，表明PNPLA1催化ω-O-酯化与亚油酸形成酰胺。此外，酰胺补充部分挽救了Pnpla1^−/−角质细胞的改变分化。我们的发现为皮肤屏障形成和鱼鳞病的发展提供了有价值的见解，并可能有助于治疗表皮屏障缺陷的新疗法策略。

• Scalable Synthesis of Human Ultralong Chain Ceramides
  作者：Lukáš Opálka、Andrej Kováčik、Michaela Sochorová、Jaroslav Roh、Jiří Kuneš、Juraj Lenčo、Kateřina Vávrová

  DOI：10.1021/acs.orglett.5b02816

  日期：2015.11.6

  Ceramides with ultralong chains (>30 carbons), also known as acylceramides, play a critical role in the survival of mammals on dry land. An efficient and scalable synthesis of four major classes of ultralong human skin ceramides is reported. The key approach involves the use of a succinimidyl ester that acts as a protective group, helps overcome the extremely low solubility, and simultaneously activates the fatty acid for its clean and high-yielding attachment to a sphingoid base.