Dendroamide A, Nostocyclamide and Related Cyclopeptides from Cyano- bacteria. Total Synthesis, together with Organised and Metal-templated Assembly from Oxazole and Thiazole- based Amino Acids

Abstract

Oxazole and thiazole-based amino acids (15-18) are shown to undergo organised and metal-templated assemblies leading to novel cyclic peptides. Thus, a 1:1:1 mixture of the amino acids (15, 16 and 17) undergo cyclisation in the presence of FDPP producing the natural hexapeptide dendroamide A (4), together with its positional isomer (33) and other cyclic trimers in a combined yield of 75%. Likewise, a mixture of 15, 16 and 18 cyclised to nostocyclamide (6), isolated from a cyanobacterium, and equal amounts of the analogues (36, 37 and 38) in a combined yield of 65%. The proportions of the cyclopeptide products produced in these novel cyclooligomerisations varied when the cyclisations were carried out in the presence of various metal ions, e.g. Cu 2 + , Ca 2 + , Na + , K + , Ag + . A brief discussion of the influence of metals in controlling the outcome of some of these reactions is given.