北島 満里子

Camptothecin (1) is well known for the remarkable inhibitory activities against tumor cells and topoisomerase I. Synthetic and biological studies about camptothecin and related compounds have been extensively carried out. In the course of chemical studies of camptothecins, we have already found that Ophiorrhiza pumila Champ. (Rubiaceae) produces not only camptothecin (1) but also a variety of related alkaloids (2-5). We herein report the synthetic studies of these alkaloids based on a biogenetic hypothesis as well as the chemical investigation of the secondary metabolites in cell cultures of this plant. I. Synthetic Studies of Camptothecin Related Compounds Vincoside lactam (8) was converted to 3(R)-deoxypumiloside tetraacetate (13) through a reductive deoxygenation at C-7 position in 3(R)-pumiloside tetraacetate (10). Synthetic 13 was identified with the tetraacetate of natural deoxypumiloside. From this result, H-3 stereochemistry of natural deoxypumiloside, which has been previously reported as α-form, was revised to be β orientation. Strictosamide (7) could also be converted to 3(S)-deoxypumiloside tetraacetate (14). By exhaustive investigation of the chemical constituents in O. pumila, it was found that O. pumila produces both of 3(R)-deoxypumiloside (16) and 3(S)-deoxypumiloside (17). II. Chemical Investigation of the Metabolites in Cell Cultures of Ophiorrhiza pumila From callus cultures induced from leaf segments of O. pumila, eight anthraquinones including two new ones and cholesterol were isolated. No trace of camptothecin related alkaloids was detected. New anthraquinones were identified as 1-hydroxy-2-hydroxymethyl-3-methoxyanthraquinone (22) and 2-butoxymethyl-1,3-dihydroxyanthraquinone (25) by spectroscopic analyses. Regenerated plant, which was formed from callus cultures through differentiation, produced camptothecin (1), pumiloside (4), 3(R)-deoxypumiloside (16), strictosamide (7) and loganin. New camptothecin alkaloid (26) was also isolated from acetylated n-BuOH fraction and identified as 9-O-β-D-glucosylcamptothecin pentaacetate (26). Hairy roots of O. pumila were obtained by the inoculation of Agrobacterium rhizogenes to regenerated plants. From hairy roots, pumiloside (4), 3(R)- and 3(S)-deoxypumiloside (16, 17), strictsamide (7), and two anthraquinones (24, 27) were isolated.