Total Synthesis of Psammaplysins A, M, O, and Q, and Ceratinamide A

The psammaplysins are a unique class of brominated marine alkaloids bearing a signature 5/7-spiroisoxazoline-oxepine core linked to a variable tyramine-derived unit. Here, we report the total synthesis of several members of this family via a dipolar cycloaddition between an in situ generated nitrile oxide and an unusual 7-membered enediol diether dipolarophile. Carefully orchestrated oxidative transformation towards the fully functionalized spirocycle and direct coupling with tyramine-derived amines provides access to five representative family members, psammaplysins A, M, O, and Q, and ceratinamide A, the latter four for the first time.