Regiocontrolled synthesis of the macrocyclic polyamine alkaloid (±)-lunarine, a time-dependent inhibitor of trypanothione reductase

A regiocontrolled synthesis of the macrocyclic polyamine alkaloid (±)-lunarine is described. The key steps involve the preparation of the differentially functionalised cis-3-oxo-8-bromo-9b-cyano-1,2,3,4,4a,9b-hexahydrobenzofuranyl tricyclic scaffold 14 which, following further elaboration, is coupled to the selectively protected acrylamidospermidine5via a Heck coupling reaction to give the pre-cyclised lunarine derivative 23.