Diastereo‐ and Enantioselective Synthesis of L‐threo‐ and D‐erythro‐Sphingosine

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Abstract
L‐threo‐sphingosine and its D‐erythro isomer (1) are subunits of many glycosphingolipids, gangliosides and ceramides. This paper describes the highly diastereo‐ and enantioselective synthesis of both isomers (de, ee > 98%). The key steps in the synthesis are the aldol reaction of the SAMP hydrazone (S)‐2 with racemic α‐phenylselenylpentadecanal 3, the diastereoselective triacetoxyborohydride reduction of ketone 5 and exclusive (E) CC double bond formation in the elimination of hydroxyl and selenyl moieties promoted by methanesulfonyl chloride. Mesylate 8 was then readily converted via the 1,3‐O‐acetonide‐protected azidosphingosine 9 to L‐threo‐sphingosine. Conversion to the known 1‐O,2‐N‐diacetyl‐protected sphingosine 13 with subsequent Mitsunobu inversion of the C3OH centre afforded the D‐erythro‐sphingosine epimer.