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.

1 - 20 . (canceled) 
     
     
         21 . A method for synthesizing N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine, comprising removing the trityl group of N-palmitoyl-1-O-trityl-3-O-benzoyl-D-erythro-sphingosine under conditions effective to yield N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine, wherein the method yields less than about 1% N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine by weight of N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine. 
     
     
         22 . The method of  claim 21 , comprising performing the following steps prior to removing the trityl group:
 allowing D-erythro-sphingosine to react with palmitic acid in the presence of O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate under conditions effective to yield N-palmitoyl-D-erythro-sphingosine;   allowing N-palmitoyl-D-erythro-sphingosine to react with a tritylating reagent under conditions effective to yield N-palmitoyl-1-O-trityl-D-erythro-sphingosine; and   allowing N-palmitoyl-1-O-trityl-D-erythro-sphingosine to react with a benzoylating reagent under conditions effective to yield N-palmitoyl-1-O-trityl-3-O-benzoyl-D-erythro-sphingosine.   
     
     
         23 . A method for synthesizing N-palmitoyl-D-erythro-sphingomyelin, comprising performing the method of  claim 21  and:
 allowing N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine to react with 2-chloro-2-oxo-1,3,2-dioxaphospholane under conditions effective to yield N-palmitoyl-3-O-benzoyl-D-erythro-1-O-(2-oxo-1,3,2-dioxaphospholane)-sphingosine; 
 allowing N-palmitoyl-3-O-benzoyl-D-erythro-1-O-(2-oxo-1,3,2-dioxaphospholane)-sphingosine to react with trimethylamine under conditions effective to yield N-palmitoyl-3-O-benzoyl-D-erythro-sphingomyelin; and 
 removing the benzoyl group of N-palmitoyl-3-O-benzoyl-D-erythro-sphingomyelin under conditions effective to yield N-palmitoyl-D-erythro-sphingomyelin. 
 
     
     
         24 . The method of  claim 23 , comprising performing the following steps prior to removing the trityl group:
 allowing D-erythro-sphingosine to react with palmitic acid in the presence of O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate under conditions effective to yield N-palmitoyl-D-erythro-sphingosine;   allowing N-palmitoyl-D-erythro-sphingosine to react with a tritylating reagent under conditions effective to yield N-palmitoyl-1-O-trityl-D-erythro-sphingosine; and   allowing N-palmitoyl-1-O-trityl-D-erythro-sphingosine to react with a benzoylating reagent under conditions effective to yield N-palmitoyl-1-O-trityl-3-O-benzoyl-D-erythro-sphingosine.   
     
     
         25 . The method of  claim 24 , wherein N-palmitoyl-D-erythro-sphingomyelin is synthesizable at an about 1 to about 50 kilogram scale. 
     
     
         26 . A composition comprising N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine and N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine, wherein the weight ratio of the N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine to the N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine is about 10:90. 
     
     
         27 . A composition comprising N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine and N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine, wherein the weight ratio of the N-palmitoyl-1-O -benzoyl-D-erythro-sphingosine to the N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine is about 5:95. 
     
     
         28 . A composition comprising N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine and N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine, wherein the weight ratio of the N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine to the N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine is about 2:98. 
     
     
         29 . A composition comprising N-palmitoyl-1-O-benzoyl-D-erythro-sphingosine and N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine, wherein the weight ratio of the N-palmitoyl-1-0-benzoyl-D-erythro-sphingosine to the N-palmitoyl-3-O-benzoyl-D-erythro-sphingosine is about 1:99.