Methods for the synthesis of sphingomyelins and dihydrosphingomyelins

Abstract

The present invention includes methods for the synthesis of sphingomyelins and dihydrosphingomyelins. The present invention also includes methods for the synthesis of sphingosines and dihydrosphingosines. The present invention further includes methods for the synthesis of ceramides and dihydroceramides.

What is claimed is: 
     
         1 . A method for synthesizing N-palmitoyl-D-erythro-dihydrosphingomyelin, comprising the steps of:
 a) allowing N-palmitoyl-D-erythro-dihydrosphingosine to react with ethylene halophosphite under conditions effective to yield N-((2S,3R)-1-((1,3,2-dioxaphospholan-2-yl)oxy)-3-hydroxyoctadecan-2-yl)palmitamide;   b) allowing N-((2S,3R)-1-((1,3,2-dioxaphospholan-2-yl)oxy)-3-hydroxyoctadecan-2-yl)palmitamide to react with bromine under conditions effective to yield 2-bromoethyl ((2S,3R)-3-hydroxy-2-palmitamidooctadecyl) phosphorobromidate; and   c) allowing 2-bromoethyl ((2S,3R)-3-hydroxy-2-palmitamidooctadecyl) phosphorobromidate to react with trimethylamine under conditions effective to yield N-palmitoyl-D-erythro-dihydrosphingomyelin.   
     
     
         2 . The method of  claim 1  wherein the ethylene halophosphite is ethylene chlorophosphite. 
     
     
         3 . A method for synthesizing N-palmitoyl-3-O-benzoyl-D-erythro-dihydrosphingomyelin, comprising the steps of:
 a) allowing N-palmitoyl-3-O-benzoyl-D-erythro-dihydrosphingosine to react with 2-chloro-2-oxo-1,3,2-dioxaphospholane (CCP) under conditions effective to yield N-palmitoyl-3-O-benzoyl-D-erythro-1-O-(2-oxo-1,3,2-dioxaphospholane)-dihydrosphingosine; and   b) allowing N-palmitoyl-3-O-benzoyl-D-erythro-1-O-(2-oxo-1,3,2-dioxaphospholane)-dihydrosphingosine to react with trimethylamine under conditions effective to yield N-palmitoyl-3-O-benzoyl-D-erythro-dihydrosphingomyelin.   
     
     
         4 . The method of  claim 3 , wherein N-palmitoyl-3-O-benzoyl-D-erythro-1-O-(2-oxo-1,3,2-dioxaphospholane)-dihydrosphingosine is not purified or isolated. 
     
     
         5 . A method for synthesizing N-palmitoyl-D-erythro-dihydrosphingomyelin, comprising performing the method of  claim 3  and allowing N-palmitoyl-3-O-benzoyl-D-erythro-dihydrosphingomyelin to react with sodium methoxide under conditions that are effective to yield N-palmitoyl-D-erythro-dihydrosphingomyelin. 
     
     
         6 . The method of  claim 3 , wherein the trimethylamine is added as a liquid. 
     
     
         7 . The method of  claim 3 , wherein the trimethylamine is added in a gaseous form. 
     
     
         8 . The method of  claim 3 , wherein the method is performed on a kilogram scale. 
     
     
         9 . The method of  claim 3 , wherein N-palmitoyl-3-O-benzoyl-D-erythro-ceramide is allowed to react with 2-chloro-2-oxo-1,3,2-dioxaphospholane in the presence of tetramethylethylenediamine.