Phosphonolipids. XX. Total synthesis of a naturally occurring ceramide aminoethylphosphonate and of its enantiomer

Abstract

The first synthesis of a naturally occurring C18-ceramide aminoethylphosphonate is described. The erythro-N-palmitoyl-D-sphingosyl-1-(2-aminoethyl)phosphonate was obtained by phosphonylation of erythro-N-palmitoyl-3-0-benzoyl-D-sphingosine with (2-phthalimidoethyl)phosphonic acid chloride and triethylamine, and consecutive removal of the protective phthaloyl and benzoyl groups of the reaction product, erythro-N-palmitoyl-3-0-benzoyl-D-sphingosyl-1-(2-phthalimidoethyl)phosphonate, by hydrazinolysis and mild alkaline hydrolysis, respectively. The unnatural l isomer was prepared in an analogous manner from erythro-N-palmitoyl-3-0-benzoyl-L-sphingosine. Comparison of the synthetic and natural ceramide aminoethylphosphonates confirmed the structure tentatively assigned by Rouser, Hori, and Hayashi and their colleagues to the C18-ceramide aminoethylphosphonates of a variety of shellfish, snails, and cephalopods, and established the fact that the natural ceramide aminoethylphosphonates are derivatives of D-sphingosine.