New approaches to synthesis of stereospecific sphingomyelin

Enormous progress in the asymmetric synthesis of stereochemically and chemi cally pure D-erythro-sphingosine and ceramides led to the development of a practical, efficient, easily scaleable process to provide industrial quanti ties of chiral sphingosine and ceramides. This established a new platform o f chiral starting materials which facilitate the synthesis of complex sphin golipids. Utilizing stereochemically homogeneous, fully synthetic ceramides , two efficient synthetic methods were developed for the preparation of ult ra pure stereochemically homogeneous sphingomyelins. The first method adapt ed highly efficient phosphoramidite technology from oligonucleotide chemist ry. This method allows selective insertion of a phosphocholine moiety into 3-O-protected ceramide through phosphitylation, followed by choline attachm ent, phosphite oxidation and deprotection. This route provides stereochemic ally homogeneous sphingomyelin in 35-79% yield. The second route is based o n the reaction of selectively protected ceramides with cyclic chlorophospha te followed by treatment with trimethylamine to give the desired sphingomye lins in 50% yield. Multigram quantities of C-14-labeled N-palmitoyl-D-eryth ro-sphingomyelin were produced with specific activity > 1000 dpm/nmol. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.