Synthesis and Metal-templated Assembly of Oxazole and Thiazole-based Amino Acids. Total Synthesis of Nostocyclamide and Related Cyclic Peptides

The oxazole and the thiazole-based amino acids, 3-5, undergo cyclisation in the presence of FDPP, producing the natural hexapeptide nostocyclamide 2 and equal amounts of the analogues, 6, 7 and 8, in a combined yield of 65%. In the presence of Cu^{2 +} ions only a 2 : 1 mixture of nostocyclamide and the cyclic peptide 6 results, and proportions of 2 are also enhanced when Li⁺ or Ca^{2 +} ions are present. Likewise, the amount of the cyclic peptide 7 increases dramatically when the three amino acids 3, 4 and 5 are mixed with FDPP in the presence of Na⁺ or K⁺ ions and in the presence of Ag⁺ ions it is the sole cyclic peptide product.

oxazole - thiazole - amino acids - nostocyclamide - cyclic peptides