Synthesis of homoceramides, novel ceramide analogues, and their lack of effect on the growth of hippocampal neurons.
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.
De Jonghe
Steven
S
Ghent University, Faculty of Pharmaceutical Sciences, Laboratory of Medicinal Chemistry, Harelbekestraat 72, 9000 Gent, Belgium.
Lamote
Inge
I
Venkataraman
Krishnan
K
Boldin
Swetlana A
SA
Hillaert
Ulrik
U
Rozenski
Jef
J
Hendrix
Chris
C
Busson
Roger
R
De Keukeleire
Denis
D
Van Calenbergh
Serge
S
Futerman
Anthony H
AH
Herdewijn
Piet
P
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002518:Ceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013057:Spectrum Analysis
D002518:Ceramides