Trichothecene analogs. 1. 1,5-Dioxaspiro[2.5]octanes

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Abstract
Seven 1,5-dioxaspiro[2.5]octanes were synthesized and tested in the mouse P388 lymphocytic leukemia screen and the mouse Ehrlich ascites screen. These compounds possess the epoxypyran structure which was believed to be the active portion of the trichothecene class of sesquiterpene tumor inhibitors. Three compounds had marginal to moderate activity in the Ehrlich ascites screen (inhibition 74.1-86.3%) and low activity in the P388 screen (T/C = 126-131). A carbocyclic analog, 1-oxaspiro[2.5]octane (9), was moderately active in both screens (inhibition 78.8%, T/C = 140). In the Ehrlich ascites screen, T-2 toxin (2) was about 25 times more potent than 9. None of the spirooctanes studied caused any skin irritation in 10 mg doses on the skin of rabbits, whereas 2 caused extensive necrosis at 0.1-mg doses.