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

Abstract

Seven l,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 has been believed to be the active portion of the trichothecene class of sesquiterpene tumor inhibitors. Three of the compounds were found to have 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 analogue, l-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.

Substituted 2-iminothiolanes: reagents for the preparation of disulfide cross-linked conjugates with increased stability

“…To a solution of 10.0 M n-BuLi (0.67 mL) in THF (10 mL) at -75 °C was added CH3CN (0.35 mL, 0.67 mmol) dropwise. After 10 min, 7-thiaspiro[5.2]octane [0.86 g, 0.67 mmol, prepared from 7-oxaspiro [5.2]octane (20) according to the method of ref 16] in 2 mL of dry THF was added.…”