New anti‐tumor agents. 1 . Heterocyclic benzodioxole lactones

Morpholino Mannich bases of types 5, 12 react with tetronic acid in aqueous acetic acid to yield uncyclized lactones of types 7, 13 . Acetylation and methylation of these products yields monoacetyl‐monomethyl derivatives which can then be cyclized in alkali to give unsaturated lactones of types 8, 16 and saturated lactones 9b, 15 . The hydroxylactone 9a can be synthesized directly by reaction of 3,4,5‐trimethoxybenzaldehyde with sesamol and tetronic acid in methanol. With few exceptions the lactones of type 8 and 16 have proven to be active inhibitors of tumor growth in the National Cancer Institute in vitro screening program against 60 diverse human cancer cell lines. The lactone 8 is particularly potent, inhibiting in vitro growth of some cancers at concentrations as low as 10 −6 ‐10 −7 moles/1.