Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
Curr Med Chem. 2010;17(21):2301-24. doi: 10.2174/092986710791331068.
Ceramides are a complex group of lipids that has gained much attention as cell signaling molecules and skin barrier constituents. In the skin, these sphingolipids form a major part of the stratum corneum intercellular lipid matrix, which is the barrier for penetration of most compounds. The development of such a protective layer was a critical step in the evolution of life on a dry land. Moreover, prominent skin diseases such as psoriasis and atopic dermatitis are associated with diminished ceramide levels and may be effectively improved by exogenous ceramides or their analogues. Since ceramides are not obtained from natural sources in pure form, they are of synthetic interest since 1950's. In this review, we describe sphingosine syntheses from 1998 until 2008, and the synthetic approaches to the unique epidermal ceramides, including the 6-hydroxysphingosine-based ones, the alpha- and omega-hydroxy forms and the omega-acyloxy species. Moreover, the structural requirements of ceramides for a competent skin barrier are discussed, including acyl chain length, trans double bond, acyl alpha-hydroxyl, stereochemistry, omega-linoleyloxy species and ceramide conformation.
神经酰胺是一类复杂的脂质，作为细胞信号分子和皮肤屏障成分备受关注。在皮肤中，这些鞘脂构成了角质层细胞间脂质基质的主要部分，是大多数化合物渗透的屏障。这种保护层的发展是陆地生命进化的关键步骤。此外，银屑病和特应性皮炎等突出的皮肤疾病与神经酰胺水平降低有关，外源性神经酰胺或其类似物可有效改善这些疾病。由于神经酰胺不能以纯形式从天然来源获得，自 20 世纪 50 年代以来，它们就具有合成意义。在这篇综述中，我们描述了 1998 年至 2008 年期间神经鞘氨醇的合成，以及独特的表皮神经酰胺的合成方法，包括基于 6-羟基神经鞘氨醇的、α-和 ω-羟基形式以及 ω-酰氧基种类。此外，还讨论了神经酰胺作为有效的皮肤屏障的结构要求，包括酰基链长度、反式双键、酰基 α-羟基、立体化学、ω-亚油酰氧基种类和神经酰胺构象。
