Phytohabitols A-C, δ-Lactone-Terminated Polyketides from an Actinomycete of the Genus Phytohabitans .

Phytohabitols A-C ( 1 - 3 ), new terminally δ-lactonized linear polyketides, were isolated from the culture extract of a rare actinomycete of the genus Phytohabitans . The structures of 1 - 3 , substituted with multiple methyl and hydroxy groups on a conjugated and a skipped diene-containing backbone, were elucidated by NMR and MS spectroscopic analyses. The absolute configuration of 1 was determined by chemical derivatization and chiral anisotropic analysis, coupled with ROESY and J -based configuration analysis. In addition, closely similar 1 H and 13 C NMR data and optical rotations among 1 - 3 supported the same stereochemistry of these polyketides. The related streptomycetes metabolites lagunapyrones B, C, and D have α-pyrone rings on the linear part in place of the δ-lactone, but their chirality at the C19-C21 stereocenters were opposite from those described here, posing a question on the previous assignment made solely by comparison of the optical rotations of four possible diastereomers. Compounds 1 - 3 inhibited migration of cancer cells with IC 50 values of 15, 11, and 8.3 μM, respectively, at noncytotoxic concentrations. In addition, 1 - 3 displayed potent antitrypanosomal activity against Trypanosoma cruzi with IC 50 values of 12, 6.4, and 18 μM, comparable to a commonly used therapeutic drug, benznidazole (IC 50 16 μM).