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New anti‐tumor agents. 1 . Heterocyclic benzodioxole lactones
Author(s) -
Jurd Leonard
Publication year - 1996
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570330438
Subject(s) - chemistry , lactone , acetylation , yield (engineering) , acetic acid , alkylation , in vitro , methanol , methylation , sesamol , organic chemistry , aqueous solution , stereochemistry , biochemistry , dna , catalysis , antioxidant , materials science , metallurgy , gene
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.