MARINE NATURAL OCCURRING 2,5-DIKETOPIPERAZINES : ISOLATION, SYNTHESIS AND OPTICAL PROPERTIES (Dedicated to Professor Isao Kuwajima on the occasion of his 77th birthday)

Abstract

Seven 2,5-diketopiperazines (DKPs) were isolated from the Fijian marine sponge Acanthella cavernosa. NMR and circular dichroism (CD) comparison with synthetic L-L DKPs allowed us to determine unambiguously the L-L absolute configuration of the natural DKPs. This work initiated the setting up of an optical properties database of natural DKPs, including specific rotation and CD. 2,5-Diketopiperazines (DKPs) are cyclic secondary metabolites directly resulted from the primary peptidic metabolites. They have been detected in beverages, foods and microorganisms. As the smallest cyclic peptides, DKPs provide interesting biological properties such as organoleptical, antitumoral, antifungal, antibacterial, antifouling and antiviral activities. 2 Many natural metabolites including alkaloids are biosynthetically derived from diketopiperazines by oxidation and rearrangement reactions. They represent an interesting tool for medicinal chemistry since their heterocyclic cores provide a good template for further chemical and stereochemical modification. Proline (Pro) and arginine (Arg) units are usually found in biologically active DKPs. Despite the increasing interest of DKPs, their stereochemical information was not well documented. DKP derivatives have attracted significant attention because of their potential rule as important class of multifunctional biomolecules. Their putative roles as signaling molecules in the chemical ecology context is more and more considered. Thus, determination of absolute configuration of cyclic dipeptides is of significant importance. As a part of our on-going research on bioactive natural compounds from Pacific Axinellidae marine sponges, a scrutinized study of secondary metabolites of a Fijian sample of the marine sponge Acanthella HETEROCYCLES, Vol. 90, No. 2, 2015 1351