DIASTEREOSELECTIVE AND ENANTIOSELECTIVE SYNTHESIS OF L-THREO-SPHINGOSINE AND D-ERYTHRO-SPHINGOSINE

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 alpha-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.