Abstract
The regioselective condensations of various 7-hydroxyisoflavonoids with bis(N,N-dimethylamino)methane in a Mannich reaction provided C-8 N,N-dimethylaminomethyl-substituted isoflavonoids in good yield. Similar condensations of 7-hydroxy-8-methylisoflavonoids led to the C-6-substituted analogs. Thermal eliminations of dimethylamine from these C-6 or C-8 N,N-dimethylaminomethyl-substituted isoflavonoids generated ortho-quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho-quinone methide intermediates trapped dienophiles including 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, 3-(N,N-dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one, 1-morpholinocyclopentene, and 1-morpholinocyclohexene to give various inverse electron-demand Diels-Alder adducts. Several adducts derived from 8-N,N-dimethylaminomethyl-substituted isoflavonoids displayed good activity in the 1-10 μm concentration range in an in vitro proliferation assay using the PC-3 prostate cancer cell line.
Original language | English |
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Pages (from-to) | 600-611 |
Number of pages | 12 |
Journal | ChemMedChem |
Volume | 11 |
Issue number | 6 |
DOIs | |
State | Published - Mar 17 2016 |
Bibliographical note
Publisher Copyright:© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keywords
- Mannich reactions
- inverse electron-demand Diels-Alder reaction
- isoflavonoids
- ortho-quinone methides
- prostate cancer PC-3 cell line
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Pharmacology
- Drug Discovery
- Pharmacology, Toxicology and Pharmaceutics (all)
- Organic Chemistry