Enantioselective Synthesis of 3-Deoxy-(R)-sphingomyelin from (S)-1-(4'-Methoxyphenyl)glycerol.

(R)-3-Deoxysphingomyelin (2) was prepared from (S)-1-(4'-methoxyphenyl)-glycerol (3). The latter was converted into either p-methoxyphenyl (PMP) (S)-oxiranylmethyl ether (5) or (R)-1-(4'-methoxyphenyl)glycerol 2,3-cyclic sulfate (6). Opening of 5 with lithium pentadecyne in the presence of BF(3).Et(2)O gave PMP (S)-2-hydroxy-4-octadecynyl ether (7) in 65% yield. Alternatively, opening of cyclic sulfate 6 with excess lithium pentadecyne in the presence of catalytic cuprous iodide, followed by acidic workup, gave 7 in 90% yield. After introduction of the amide group via azide displacement, reduction, and N-acylation, simultaneous reduction of the triple bond and deprotection of the PMP group by Birch reduction (Li, EtNH(2)) provided 3-deoxy-N-palmitoyl-(R)-ceramide (9). Finally, phosphitylation of 9, oxidation of the cyclic phosphite with bromine, followed by in situ ring opening gave a (2-bromoethyl)phosphate ester, which on quaternization with aqueous trimethylamine afforded 3-deoxy-N-palmitoyl-(R)-sphingomyelin (2) in 49% overall yield from PMP (S)-2-hydroxy-4-octadecynyl ether (7).