A library of 64 phytosphingolipid analogues resulting from the systematic variation of the C1, C3, C4, and the N-acyl moiety of phytosphingosine (PHS) has been prepared from common scaffolds derived from the chiral pool and Sharpless asymmetric dihydroxylation reactions. Library members have been evaluated as growth inhibitors of the yeast Saccaromyces cerevisiae. In addition, 1-amino-N-pivaloyl PHS analogues were also tested as IPC synthase inhibitors, in comparison with the natural product khafrefungin.