Application of Mannich bases to the synthesis of hydroxymethylated isoflavonoids as potential antineoplastic agentsElectronic supplementary information (ESI) available: Copies of NMR data for all synthesized compounds are available online. See DOI: 10.1039/c5ob01828e

• Main Authors: Frasinyuk, Mykhaylo S, Mrug, Galyna P, Bondarenko, Svitlana P, Sviripa, Vitaliy M, Zhang, Wen, Cai, Xianfeng, Fiandalo, Michael V, Mohler, James L, Liu, Chunming, Watt, David S
• Format: Journal Article
• Language: English
• Published: 17.11.2015
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob01828e

The regiospecific Mannich aminomethylation of 7-hydroxyisoflavonoids using bis( N , N -dimethylamino)methane afforded C-8 substituted N , N -dimethylaminomethyl adducts, and the regioselective aminomethylation of 5-hydroxy-7-methoxyisoflavonoids afforded predominantly the C-6 substituted N , N -dimethylaminomethyl adducts. Acetylation of these C-6 or C-8 Mannich bases with potassium acetate in acetic anhydride provided access to the corresponding acetoxymethyl derivatives that were subsequently converted to hydroxymethyl- and methoxymethyl-substituted 5-hydroxy- or 7-hydroxyisoflavonoids related to naturally occurring flavonoids. The C-8 acetoxymethyl, hydroxymethyl or methoxymethyl-substituted isoflavonoids possessed promising inhibitory potency in the low micromolar range in a prostate cancer PC-3 cell proliferation assay. C-6 and C-8 Hydroxy-, acetoxy- and alkoxymethyl derivatives of isoflavones were synthesized from Mannich bases and show inhibition in the low micromolar range in a prostate cancer PC3 cell line.