TUMOR INHIBITORS .45. CROTEPOXIDE, A NOVEL CYCLOHEXANE DIEPOXIDE TUMOR INHIBITOR FROM CROTON MACROSTACHYS

An alcoholic extract of the fruits of Croton macrostachys Hdchst. ex A. Rich, was found to show significant inhibitory activity against the Lewis lung carcinoma in mice (LL). The major active component, crotepoxide (1), C18H18O8, was isolated and found to be a novel cyclohexane diepoxide. Alkaline hydrolysis and spectral evidence showed it to be the benzoate and diacetate derivative of the triol 2. Hydrogenation of 1 reduced the aromatic ring to give a hexahydro derivative 3. On treatment with hydrochloric acid, crotepoxide yielded initially the monochlorohydrin 4, and then the dideacetyldichlorohydrin 5. Treatment of 1 with hydriodic acid yielded the iodohydrin 8 and the ene diol 9, whose reactivity has been studied. The structure and absolute stereochemistry of 8 were established by X-ray crystallographic analysis and, together with spectral evidence, were used to confirm the absolute stereochemistry and structure of 1. © 1969, American Chemical Society. All rights reserved.