Study of Effect of Ceramide Hydroxylation on Permeability and Microstructure of Model Lipid Membranes

Charles University, Faculty of Pharmacy in Hradec Králové Department of Department of Organic and Bioorganic Chemistry Candidate Mgr. Andrej Kováčik Supervisor prof. PharmDr. Kateřina Vávrová, Ph.D. Title of Doctoral Thesis Study of Effect of Ceramide Hydroxylation on Permeability and Microstructure of Model Lipid Membranes Ceramides (Cer) occur in intracellular spaces of the stratum corneum, the outermost mammalian epidermal layer, where they along with other lipids (free fatty acids, cholesterol) form a skin lipid barrier. Besides sphingosine- (Cer NS) and dihydrosphingosine-based Cer (Cer NdS), in the healthy mammalian epidermis some polar Cer are present, i.e., Cer based on phytosphingosine (with hydroxyl group in position 4, i.e., phytoceramides) and Cer based on 6-hydroxysphingosine (with hydroxyl group in position 6, i.e., 6- hydroxyceramides). However, the role of phytoceramides (Cer NP) and 6 hydroxyceramides (Cer NH) in the skin barrier function has not been clarified. Moreover, 6 hydroxyceramides are not commercially available. Therefore, the first aim of this work was to synthesize physiological 6-hydroxyceramides. The synthesis of 6- hydroxylated Cer, i.e., Cer NH with long (C24:0) and Cer EOH with ultralong acyl with ester-linked linoleic acid is reported. The triple bond was reduced..