Organocatalytic Synthesis of Sphingoids

Significance

The key intermediate 5 for the total synthesis of d-arabino-phytosphingosine (1) and l-ribo-phytosphingosine (2) was obtained via (S)-proline-catalyzed aldol reaction of dioxanone 3 and pentadecanal 4 in good yield (60%) and excellent diastereo- and enantioselectivities (>99% de, 95% ee). Aldol 5 was converted into d-arabino-phytosphingosine (1) in 51% overall yield (6 steps) via straightforward reductive amination chemistry. l-ribo-Phytosphingosine (2) was obtained in a total eight steps and in an isolated 36% overall yield using a similar sequence.