Sphingosines - an Oxa-Cope Rearrangement Route for Their Synthesis

Various methods for the synthesis of sphingosine (1) and phytosphingosine (2) have been reported. Some are based on starting materials derived from the chiral pool. In this paper, it is demonstrated that the generally required trans-selective C=C bond formation, with concomitant chain extension and the introduction of the amino group, can be achieved starting from 2,4-di-O-protected D-threose 6, itself readily available from D-galactose. For instance, the sequence vinylmagnesium bromide addition to 6 (→ 7a, x), regioselective 3-O-mesylation (→ 8a, x), oxa-Cope rearrangement by treatment with trimethyl orthoacetate (→ 9), azido group introduction (→ 14), deprotection, and azido group reduction, yields the novel sphingosine 17. Oxa-Cope rearrangements with other ortho esters and with 3-O-benzoyl-protected vinylcarbinol precursors 22a, x were also investigated, for instance, for the synthesis of truncated sphingosines.

sphingosine - phytosphinganine - synthesis - oxa-Cope rearrangement - chiral pool