The structure of amoorastatone and the cytotoxic limonoid 12-hydroxyamoorastatin

Summary 2 new limonoid-type terpenes have been isolated from an aqueous extract of seeds produced by the Eastern Himalayan (India) plantAphanamixis grandifolia Bl. By interpreting principally mass spectral and nuclear magnetic resonance data, the structures of 12-hydroxyamoorastatin (2b) and amoorastatone (3) were elucidated. Unequivocal evidence for the 12-hydroxyamoorastatin structural assignment was obtained by chemical conversion to sendanin (4). Amoorastatin derivative2b was found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell lines but amoorastatone in the same system was inactive. In a comparative biological study, sendanin (4) and anthothecol (7) were also found significantly to inhibit growth of the P388 cell line, while rohitukin (8) and limonin (9) were found to be inactive.Part 63 of the series Antineoplastic Agents. For the previous contribution refer to G.R. Pettit, T.S. Krupa and R.M. Reynolds, Int. J. Peptide Protein Res., in preparation. The present investigation was supported in part by Public Health Research Grant No. CA-16049-05 from the National Cancer Institute, the Fannie E. Rippel Foundation, Mrs Mary Dell Pritzlaff, the Spencer T. and Ann W. Olin Foundation, Mr John F. Schmidt, and the Phoenix Coca-Cola Bottling Company.