Synthesis and Structure-Activity Relationships of Skin Ceramides

Abstract

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.

Amino acid derivatives as transdermal permeation enhancers

“…The double-chain compounds were designed to resemble ceramides (neutral sphingolipids in the SC intercellular lipid lamellae [51,52]), which are believed to be important targets of the enhancers [2,3]. The 12C chains were selected based on previous studies showing that this particular length was optimal for high enhancing activity [7][8][9][10][11][12][13][14]; for reviews, see [1,6,15].…”

Probing the Role of the Ceramide Acyl Chain Length and Sphingosine Unsaturation in Model Skin Barrier Lipid Mixtures by 2H Solid-State NMR Spectroscopy

“…2,3 For the therapy of these conditions, topical supplementation of Cer or their less-expensive analogs is an interesting opportunity, 4 which is, however, limited by the fact that the structural requirements and behavior of Cer are not fully known. 5 DihydroCer, i.e., the sphingolipid species that lack the C4 trans double bond such as nonhydroxy acyl dihydroCer (Cer [NDS]), are biosynthetic precursors of Cer ( Figure 1). 6 They have been detected in the SC only recently, 7 and their function in skin barrier homeostasis is unknown.…”

The Skin Microbiome in Atopic Dermatitis and Its Relationship to Emollients

“…[15][16]2014. Exclusion criteria were published literature prior to 2000 and a publication language other than English, German, or French.…”