Synthesis of the 1,2,4-thiadiazole alkaloids polycarpathiamines A and B

Abstract

In the presence of 1 mol% of a copper(II) catalyst and air, a readily available N¹-acetyl-N³-thioacylguanidine undergoes a one-pot benzylic oxidation–oxidative heterocyclization sequence to give the 3-amino-5-acyl-1,2,4-thiadiazole core of polycarpathiamines A (2) and B (3) and thus facilitating the first synthesis of both natural products. This methodology offers a straightforward alternative to the low yielding dipolar cycloaddition used to access 3-amino-5-acyl-1,2,4-thiadiazoles.