Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases

作者：Frasinyuk Mykhaylo S^*; Mrug Galyna P; Bondarenko Svitlana P; Khilya Volodymyr P; Sviripa Vitaliy M; Syrotchuk Oleksandr A; Zhang Wen; Cai Xianfeng; Fiandalo Michael V; Mohler James L; Liu Chunming; Watt David S^*

来源：ChemMedChem, 2016, 11(6): 600-611.

DOI：10.1002/cmdc.201600008

• inverse electron-demand Diels-Alder reaction
• isoflavonoids
• Mannich reactions
• ortho-quinone methides
• prostate cancer PC-3 cell line

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 1-10m concentration range in an in vitro proliferation assay using the PC-3 prostate cancer cell line.

• 出版日期2016-3-17