TY - JOUR
T1 - Application of Mannich bases to the synthesis of hydroxymethylated isoflavonoids as potential antineoplastic agents
AU - Frasinyuk, Mykhaylo S.
AU - Mrug, Galyna P.
AU - Bondarenko, Svitlana P.
AU - Sviripa, Vitaliy M.
AU - Zhang, Wen
AU - Cai, Xianfeng
AU - Fiandalo, Michael V.
AU - Mohler, James L.
AU - Liu, Chunming
AU - Watt, David S.
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2015/9/23
Y1 - 2015/9/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84947723373&partnerID=8YFLogxK
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U2 - 10.1039/c5ob01828e
DO - 10.1039/c5ob01828e
M3 - Article
C2 - 26416505
AN - SCOPUS:84947723373
SN - 1477-0520
VL - 13
SP - 11292
EP - 11301
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 46
ER -
