Three new synthetic equivalents containing Weinreb amide functionality for the central core of FTY720, an immunosuppressive agent, have been developed. These synthetic equivalents enabled incorporation of the polar head group of FTY720, through Julia, Wittig, and Horner-Wadsworth-Emmons reactions and also allowed for variation in the chain length of the lipophilic side chain in target, through the Weinreb amide functionality therein. The use of tris(hydroxymethyl)aminomethane, commercially available at low cost for the polar head group offers a distinct advantage. Convenient reactions and simple functional group interconversions in good to high yield highlight the strength of the new route developed for the synthesis of clinically important FTY720. © Georg Thieme Verlag Stuttgart.