A mechanism-based sphingosine-1-phosphate lyase inhibitor

The synthesis of a series of vinylated analogs of sphingosine-1-phosphate, together with their unambiguous configurational assignment by VCD methods is reported. Among them, compound RBM10-8 can irreversibly inhibit human sphingosine 1 phosphate lyase (hS1PL), while behaving also as an enzyme substrate. These findings, together with the postulated mechanism for S1PL activity, reinforce the role of RBM10-8 as a new mechanism-based hS1PL inhibitor.