A new approach to the stereo selective total synthesis of isotopically labeled D-ribo-phytosphingosine

摘要

We describe a novel stereoselective total synthesis of D-ribo-[1,1-~2H-1,2-~(13)C]phytosphingosine (12). Chirality at the incipient C-4 position was derived from asymmetric dihydroxylation of 1-hexadecene. The remaining chiral centers were formed by Sharpless epoxidation of an allylic alcohol, followed by benzoylcarbamate cyclization to furnish a 2-amino-1,3,4-triol derivative with the desired stereochemistry. The ~2H and ~(13)C labels were introduced by Horner-Emmons condensation of ~(13)C-labeled triethyl phosphonoacetate, followed by reduction of the resulting carboxylic ester with AlCl_3/LiAlD_4. Mass spectral results indicated the suitability of 12 as an internal standard for analyses by the isotope dilution method.