Synthesis of homoceramides, novel ceramide analogues, and their lack of effect on the growth of hippocampal neurons
De Jonghe, Steven × Lamote, Inge Venkataraman, Krishnan Boldin, Swetlana A Hillaert, Ulrik Rozenski, Jef Hendrix, Chris Busson, Roger De Keukeleire, Denis Van Calenbergh, Serge Futerman, Anthony H Herdewijn, Piet #
Journal of Organic Chemistry vol:67 issue:3 pages:988-996
The synthesis of a new series of D-erythro-homoceramide analogues is described. Several synthetic approaches were investigated. Homoceramides can be successfully synthesized from L-homoserine as chiral building block and a protected Weinreb-amide as a key intermediate. The synthesis of short-chain analogues with a heptyl side chain, as well as with a phenyl residue in the sphingoid part (instead of the naturally occurring tridecyl side chain), was effected. The homoceramides 15-17 and 24 were investigated for their potential to reverse the inhibitory effect of fumonisin B(1) on axonal growth. Unfortunately, none of the tested compounds showed any biological activity due to their lack of metabolism to glucosylhomoceramide.