Bioactive labdane diterpenoids from Renealmia alpinia collected in the Suriname rainforest

Abstract

The preservation of tropical rainforests is an important goal both for the intrinsic value of their cultural and biological diversity as well as for the well-being of the peoples who make these forests their home. In addition, tropical forests are potential sources of new pharmaceutical products that can only be found by chemical prospecting in Nature's genetically encoded combinatorial library. As part of an effort to integrate biodiversity conservation and drug discovery with economic development, we have initiated a collaborative program to discover potential pharmaceuticals in the rainforest of Suriname. The plant Renealmia alpinia (Zingiberaceae) was selected for investigation based on its ethnomedical use as a febrifuge, but testing in the yeast Sc-7 assay gave a positive response, indicative of cytotoxic activity. Using this bioassay, the two new labdane diterpense, 11-hydroxy-8(17),12(E)-labdadien-15,-16-dial 11,15-hemiacetal (1) and 16-oxo-8(17),12(E)-labdadien-15-oic acid (2), and the known diterpene, 8(17),12(E)-labdadien-15,16-dial (3), have been isolated. Their structures were elucidated by 1D and 2D NMR techniques (DEPT, COSY, HETCOR, HMBC, and NOESY) and IR, UV, and MS spectra, and the absolute stereochemistry of 1 was established by CD spectroscopy and by the formation and NMR analysis of alpha-methoxyphenylacetyl esters. The hemiacetal 1 was cytotoxic to M109 cells, with an IC50 value of 2.6 micrograms/mL.