title: Methanolysis of sphingomyelin. Toward an epimerization-free methodology for the preparation of D-erythro-sphingosylphosphocholine.
abstract: It is well known that acid hydrolysis of natural sphingomyelin in aqueous methanol or 1-butanol at refluxing temperature is accompanied by epimerization at the C-3 position of the long-chain base. An improved procedure for the hydrolysis of commercially available, naturally occurring sphingomyelin is described. Prolonged exposure (3;-4 days) of sphingomyelin to freshly prepared 0.5 M anhydrous methanolic hydrogen chloride (generated by trapping the gas evolved from the reaction of concentrated sulfuric acid with solid sodium chloride in anhydrous methanol) at 50 degrees C resulted in cleavage of the amide side chain. The extent of epimerization of the allylic alcohol stereocenter was quantified by integration of the C-5 signal of the (13)C nuclear magnetic resonance spectrum of lysosphingomyelin. The method described here is superior to the traditional acid hydrolysis methods because it provides the product as a approximately 10:1 ratio of d-erythro/l-threo epimers; in contrast, a ratio of approximately 1. 3:1 was obtained by the previous methods. We also report that use of dichloromethane as a cosolvent with N,N-dimethylformamide in the reaction of lysosphingomyelin with an activated fatty acid reduced the time required for completion of the N-acylation reaction.
authors: Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, NY 11367, USA.
authors: R
authors: R
authors: Bittman
authors: C A
authors: CA
authors: Verbicky
mesh_terms: D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013109:Sphingomyelins / Q000737:chemistry*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D013109:Sphingomyelins; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D013110:Sphingosine; D008697:Methane