The biosynthetic origin of diketopiperazines derived from D-proline

Investigations reveal that the structures assigned to D-a-amino acid containing diketopiperazines (DKPs) 21-25 isolated from the sponge Calyx CE podatypa have been reported incorrectly. Synthetic studies and comparison with literature data have enabled the structures of these DKPs to be correctly reassigned. Evidence is presented to suggest that naturally occurring D-Pro-L-Xxx-DKPs are artifacts resulting from non-enzymatic epimerisation of the corresponding L-Pro-L-Xxx-DKP natural products.