Synthesis of Sphingadienine-type Glucocerebrosides

Sphinga-4,8-dienine derivatives were synthesized from a vinyl-epoxide 5 via three routes. First, reaction of 5 with 2-dodecenyl cyanocuprate afforded a 1:1 mixture of (4E,8E)- and (4E,8Z)-sphingadienine derivatives in high yield. Second, the (4E,8E)-isomer was selectively synthesized via allylic bromide-allylic sulfone coupling followed by desulfonylation. Third, the (4E,8Z)-isomer was selectively synthesized via SN2′-type addition of di(cyanomethyl)copper-lithium followed by Wittig olefination. These synthetic intermediates were converted to sphingadienine-type glucocerebrosides 1a and 1b which have calcium ionophoretic activity.