Methods for the synthesis of sphingomyelins and dihydrosphingomyelins

A method for synthesizing a sphingomyelin comprising:

• a) acylating sphingosine with a fatty acid;
• b) protecting the primary hydroxyl group of the product of step a) with a trityl group;
• c) protecting the secondary hydroxyl group of the product of step b) with a benzoyl group;
• d) removing the trityl group;
• e) reacting the product of step d) with 2-chloro-2-oxo-1,3,2-dioxaphospholane (CCP);
• f) reacting the product of step e) with trimethylamine;
• and
• g) removing the benzoyl group to yield the sphingomyelin.

A method of synthesizing N-acyl-D erythro-sphingomyelin, comprising the steps of:

• a) phosphitylating a N-acyl-D-erythro-sphingosine with an ethylene halophosphite in the presence of a base and in the presence of an aprotic polar solvent having a dielectric constant of greater than 20;
• b) adding an alcohol in an amount to quench any unreacted ethylene halophosphite;
• c) adding bromine to the product of step a);
• and
• d) quaternizing the product of step c) with trimethylamine to yield the N-acyl-D-erythro-sphingomyelin.

A method for synthesizing an N-acyl-D-erythro-sphingomyelin, comprising the steps of:

• a) reacting D-erythro-3-O-benzoylceramide with 2-chloro-2-oxo-1,3,2-dioxaphospholane (CCP) to yield D-erythro-3-O-benzoyl-1-O-(2-oxo-1,3,2-dioxaphospholane)ceramide;
• b) reacting D-erythro-3-O-benzoyl-1-O-(2-oxo-1,3,2-dioxaphospholane)ceramide with trimethylamine to yield an N-acyl-D-erythro-3-O-benzoylsphingomyelin;
• and
• c) removing the benzoyl group of the N-acyl-D-erythro-3-β-benzoylsphingomyelin with sodium methoxide to yield an N-acyl-D-erythro-sphingomyelin.