Gram-Scale Synthesis of Chain-Deuterated Sphingosine and Its Derivatization to Produce Ceramide,Sphinganine and Sphingosine-1-phosphate

Sphingosine plays crucial roles in various cellular functions. Deuterated molecules are widely used as the important tools to explore the structure, property, and function of biochemical materials. We here report a gram-scale synthesis of sphingosines with different deuterated chains. The synthesis started from different protiated fatty acids, which underwent hydrothermal platinum-catalyzed hydrogen/deuterium (H/D) exchange to produce the deuterated chains with different length. The Horner–Wadsworth–Emmons (HWE) coupling of a chiral amino acid derivative with the deuterated chains generated the unsaturated ketone precursors. The following stereoselective reduction via cyclic Felkin–Anh transition led to the desired anti-amino alcohol geometry. This efficient protocol enabled the gram-scale synthesis of the chain-deuterated sphingosines. The subsequent synthesis of the chain-deuterated derivatives, i. e. ceramide, sphinganine and sphingosine-1-phosphate, is also described. Their deuterium content was simultaneously characterized by ¹H NMR and high-resolution mass spectrum (HRMS).