Synthesis of D‐Erythro‐ and D‐Threo‐Sphingosine Derivatives From L‐Serine

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Abstract
The protected serine aldehyde 10 was converted to the crystalline N‐Boc‐protected sphingosines 6–9 by a three‐step reaction sequence. Compound 10 was transformed with high diastereoselectivity (95%) either to the erythro‐ or threo‐alkynols, 17 and 18, respectively. The erythro‐isomer 17 is formed by the addition to 10 of lithium pentadecyne 16 in THF/HMPT at −78°, whereas the corresponding threo‐isomer 18 is produced in the presence of ZnBr2 in Et2O. Deprotection of the acetal moiety afforded 1,3‐diols 19 and 20. These diols were selectively reduced with Red‐Al to the (E)‐sphingosines 6 and 8, or the (Z)‐isomers 7 and 9 by partial hydrogenation over Lindlar's catalyst. Cleavage of the N‐Boc group and further transformation to ceramides were readily achieved as demonstarted by the conversion of 6 to N‐octadecanoyl‐D‐erythro‐sphingosine 5.