Bioactive diketopiperazines and nucleoside derivatives from a sponge-derived Streptomyces species

Abstract

Fractionation and purification of the ethyl acetate extract of the culture of a sponge-derived actinomycete, Streptomyces species Call-36, resulted in the isolation and identification of a new diketopiperazine, actinozine A (1), cyclo(2-OH-d-Pro-l-Leu) (2), two new nucleosides, thymidine-3-mercaptocarbamic acid (3) and thymidine-3-thioamine (4), together with cyclo(d-Pro-l-Phe) (5) and cyclo(l-Pro-l-Phe) (6). The structure assignments of the compounds were carried out by interpretation of 1D and 2D NMR data and mass spectral determinations. The absolute configurations of 1 and 2 were determined by Marfey’s method and by comparison of the experimental and TDDFT-calculated ECD spectra. Actinozine A possesses an unprecedented hydroperoxy moiety at C-2 of the proline moiety, while 3 and 4 possess unusual mercaptocarbamic acid and thiohydroxylamine functionalities at N-3 of the thymine moiety. The isolated compounds displayed variable cytotoxic and antimicrobial activities.