A series of 9-O-acylisoaaptamine (3-14) and 4-N-acyl-dihydroaaptamine (16-19) derivatives have been prepared and evaluated for antitumor activity against murine P-388 and human tumor cells including KB16, A549, and HT-29 cell lines. All of compounds showed significant cytotoxicity against P-388 cells. Among them, compounds 9-11 showed potent activity as isoaaptamine (1). There was an apparent lack of linear relationship between cytotoxicity and carbon number of the side chain. The structure and activity relationship for these particular compounds are discussed.

Bioassay-guided fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7). The structures of 1-6 were established on the basis of extensive 1D and 2D NMR spectroscopic analysis. In addition, the new derivatives, 8 and 9, were prepared by acylation of 7 and 3, respectively. The isolated diterpenoids and their derivatives were tested against human prostate (PC-3) and hepatoma (Hep3B) cancer cells. Compounds 1, 3-5, and 7 exhibited cytotoxicity against both tumor cells, with IC(50) values below 3 micromicro, while compounds 2, 6, 8, and 9 were less effective.

A recent study of the EtOAc extract of the gorgonian Briareum excavatum afforded six new diterpenes of the briarane skeleton, excavatolides U-Z (1-6). The structures and relative stereochemistry of metabolites 1-6 were assigned on the basis of NMR studies and chemical methods. The structure, including the relative configuration of excavatolide U (1), was further confirmed by a single-crystal X-ray analysis. Some of the excavatolides have displayed significant cytotoxicity toward P-388 and HT-29 tumor cells.