Jeremy M. Sivak

Two stereocontrolled, efficient, and modular syntheses of eicosanoid lipoxin B4 (LXB 4 ) are reported. One features a stereoselective reduction followed by an asymmetric epoxidation sequence to set the vicinal diol stereocentres. The dienyne was installed via a one‐pot Wittig olefination and base‐mediated epoxide ring opening cascade. The other approach installed the diol through an asymmetric dihydroxylation reaction followed by a Horner‐Wadsworth‐Emmons olefination to afford the common dienyne intermediate. Finally, a Sonogashira coupling and an alkyne hydrosilylation/proto‐desilylation protocol furnished LXB 4 in 25 % overall yield in just 10 steps. For the first time, LXB 4 has been fully characterized spectroscopically with its structure confirmed as previously reported. We have demonstrated that the synthesized LXB 4 showed similar biological activity to commercial sources in a cellular neuroprotection model. This synthetic route can be employed to synthesize large quantities of LXB 4 , enable synthesis of new analogs, and chemical probes for receptor and pathway characterization.