Synthesis of Unique Ceramides and Cerebrosides Occurring in Human Epidermis

✍ Scribed by Siliva Müller; Richard R. Schmidt

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: German
• Weight: 984 KB
• Volume: 76
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19930760141

✦ Synopsis

The sphingolipids la, b and 2a, b, which play important roles in epidermal barrier function, were synthesized by N-acylation of C,,-sphingosine 3 and I-0-glucosylated C,,-sphingosine 6, respectively, with w-acyloxy-substituted fatty acids 4 and 5 (Scheme 1 ) . These fatty acids were obtained from w-hydroxy-substituted fatty acids 8 and 9 by esterification with linoleic acid (7). The C,,-fatty acid 8 was prepared as follows: C,,-Compound 18 was obtained by means of a Wittig reaction of C,,-aldehyde 13 with C,,-phosphoniurn salt 15 or of CI2-aldehyde 24 with C,,-phosphonium salt 21, respectively, and subsequent hydrogenation and U-deprotection (Scheme 2). Alternatively, 8 was prepared via 30 by copper-catalyzed coupling of C,,-alkyl halide 19 with the Grignurdreagent derived from C,,-alkyl bromide 14 (Scheme 2). Oxidation of 18 to aldehyde 39 and Wittig reaction with C9-phosphonium salt 41 furnished the desired w-hydroxy-substituted fatty acid 8, after 0-deprotection (Scheme 3). Similarly, Wirtig reaction of C, ,-phosphonium salt 22 with C,,-aldehyde 24 furnished C,,-aldehyde 40, after hydrogenation, O-deprotection, and oxidation; Wittig reaction with compound 41 and subsequent deprotection afforded the desired C,,-fatty acid 9 (Scheme 3). An alternative strategy furnished compound 8 by a coupling reaction of alkyne 53 with w-bromo-substituted fatty acid 52, obtained from compounds 24 and 47 by Wittig reaction, hydrogenation, and introduction of bromide (Scheme 4). Hydrogenation (Lindlar's catalyst) of the resulting C34-alkyne 54 and deprotection furnished 8. *) For a synthesis of 50 via a different strategy, see [24]. 24 46 X = B r 47 X = Ph3P.z] MeOOC-(CH,)r(CH,),,-CH,O Ac 48 d ) e) ' HCEC-(CH,),-CH,O(Thp)