Plant Antitumor Agents, 26. Isolation, Structure, and Antitumor Activity of Alkaloids from Anopterus glandulosus

Journal of Natural Products
1987.0

Abstract

During our studies of plants with cytotoxic (KB) activity or life-prolongation activity in mouse leukemia assays (P-388 or L-1210), it was found that a crude EtOH extract of Anopterus glandulosus Labill. (Escalloniaceae) exhibited high activity in the P-388 (T/C 193 at 50 mg/kg) and KB (ED₅₀ 5×10⁻¹ µg/ml) systems, and, consequently, fractionation studies were initiated. There are only two known Anopterus species, both restricted in distribution to Australia, Anopterus maleuyanus F. Muell. is a tree found in southern Queensland, and A. glandulosus is a small Tasmanian tree. The alkaloids of A. maleuyanus were first examined by Hart et al. (1,2) who discovered several novel bases with an ent-kaurenoid skeleton. Although the alkaloids were reported to have activity in the KB and P-388 assays, no details were presented (1), and no bases were isolated in crystalline form from A. glandulosus, which has a much lower alkaloid content. More recently we have presented a preliminary report of the alkaloids of A. glandulosus (3). Subsequently a 2D-nmr study by Johns et al. (4) has clarified the uncertain position of one hydroxyl group present in some of the bases. In this report we present a full account of the isolation and structure-activity relationships found in the ent-kaurene alkaloids isolated from A. glandulosus, including the isolation of two new bases. Details of structural elucidation will be limited because all of the compounds 1-5 have now been described (1,2,4). The observed biological activity was not due to the non-alkaloidal components as this fraction was inactive in the KB and P-388 test systems.

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