神经酰胺,细胞生物学中至关重要的鞘脂,发挥各种作用,从结构膜完整性到信号通路调节。在结构上,神经酰胺由与鞘氨醇碱相连的脂肪酸组成。脂肪酸链的特点,包括长度和饱和度,确定神经酰胺的生理特性。根据链长,神经酰胺通常分为以下类别:中等,长,很长,超长。其中,两种超长链神经酰胺,Cer(24:1(15Z))和Cer(24:0),已经被广泛研究,它们以其调节功能而闻名。然而,神经酰胺的疏水性,由它们的长的烃链产生的阻碍了它们的溶解度和细胞递送水平。尽管已经开发了ω-吡啶鎓神经酰胺类似物(ω-PyrCers)来解决这个问题,具有非常长的脂肪酸链或不饱和度的ω-PyrCers尚未开发,可能是由于获得合成所需的相应ω-溴脂肪酸的途径有限。在这项研究中,我们准备了Cer(24:1(15Z))和Cer(24:0)的ω-PyrCers,PyrCer(24:1(15Z))和PyrCer(24:0),分别。合成中的关键是Wittig反应以制备具有适当链长和(Z)-双键位置的ω-溴脂肪酸。对PyrCer(24:1(15Z))和PyrCer(24:0)的初步评估揭示了它们在肝细胞癌治疗中的潜力。
Ceramides, crucial sphingolipids in cellular biology, play various roles ranging from structural membrane integrity to signaling pathway regulation. Structurally, a ceramide consists of a fatty acid connected to a sphingoid base. The characteristics of the fatty acid chain, including length and saturation, determine the physiological properties of the ceramide. Ceramides typically fall into the following categories based on chain length: medium, long, very-long, and ultra-long. Among them, two very-long-chain ceramides, Cer(24:1(15Z)) and Cer(24:0), have been extensively studied, and they are known for their regulatory functions. However, the hydrophobic natures of ceramides, arising from their long hydrocarbon chain impedes their solubilities and levels of cellular delivery. Although ω-pyridinium ceramide analogs (ω-PyrCers) have been developed to address this issue, ω-PyrCers with very-long fatty acid chains or unsaturation have not been developed, presumably due to limited access to the corresponding ω-bromo fatty acids required in their syntheses. In this study, we prepared the ω-PyrCers of Cer(24:1(15Z)) and Cer(24:0), PyrCer(24:1(15Z)) and PyrCer(24:0), respectively. The key in the synthesis is the Wittig reaction to prepare the ω-bromo fatty acid with an appropriate chain length and (Z)-double bond position. Preliminary evaluation of the PyrCer(24:1(15Z)) and PyrCer(24:0) revealed their potential in hepatocellular carcinoma treatment.