Antineoplastic Agents. 529. Isolation and Structure of Nootkastatins 1 and 2 from the Alaskan Yellow CedarChamaecyparisnootkatensis

Abstract

The yellow cedar tree, Chamaecyparis nootkatensis, collected in southeast Alaska was evaluated as a potential source of new anticancer agents. Two new diterpene anticancer constituents termed nootkastatins 1 (4) and 2 (5) were isolated along with three previously known diterpene cancer cell growth inhibitors where two were reported as synthetic modifications of totarol and not previously found in nature. All five diterpene structures were established by HRMS and 1D and 2D NMR spectroscopic analyses combined with three X-ray crystal structure determinations (2, 3, and 5). Against a panel of six human cancer cell lines, this series of diterpenes exhibited inhibition over the range GI₅₀ 0.75−2.0 μg/mL, and all inhibited the growth of Gram-positive bacteria and fungi.