Synthesis of the 1,2,4-Thiadiazole Alkaloid Polyaurine B.

A short synthesis of the natural product polyaurine B is described. The 1,2,4-thiadiazole heterocycle was assembled using a Cu(II)-mediated heterocyclization reaction that forges the N-S bond. The final acylation step to install the methylcarbamate must be conducted under anhydrous, nonbasic conditions to prevent thiadiazole ring opening initiated by attack of hydroxide at C-5.