New flavonoid-containing derivatives of lupinine

• DOI: 10.1007/s10600-012-0212-6
• Publication Date: 2012-05-15T02:50:26Z
• Authors: S. P. Bondarenko; M. S. Frasinyuk; A. I. Galaev; V. I. Vinogradova
• Keywords: Moiety; Benzopyrans

An oxazine ring was annelated to benzopyran-4-one and benzopyran-2-one cores by reacting 7-hydroxyisoflavones and 7-hydroxycoumarins with lupinylamine and formalin. The new derivatives 9,10-dihydro- 4H,8H-chromeno(8,7-e)(1,3)oxazin-4-one and 9,10-dihydro-2H,8H-chromeno(8,7-e)(1,3)oxazin-2-one containing a lupinine moiety in the 9-position were prepared. The presence of a hydroxyl in lupinine enabled several esters of carboxylic and dicarboxylic acids (3-5) with antiviral, antitumor, hepatoprotective, antituberculosis, anticholinesterase, and anesthetic properties (6, 7) to be prepared from it. A series of new derivatives of 4-aminoquinoline that included a lupinylamine moiety (2) exhibited antimalarial activity (8). Salts of lupinine with 3- or 4-azomethinebenzoic acids were also synthesized (9). Several azomethines of lupinylamine (10) and its phosphorylated derivatives (11) were prepared. The goal of the present work was to introduce the lupinine moiety into natural flavonoids and their analogs because the combination in one molecule of two natural heterocyclic groups could facilitate the manifestation of properties important for practical use. The appropriate ratio of substrate, amine, and formaldehyde in the presence of a basic catalyst under Mannich reaction conditions is known to form derivatives of 3,4-dihydro-1,3-benzoxazines as a result of electrophilic substitution (12-14). We considered it interesting to study the reaction features of flavonoids with lupinylamine and formalin. Heating formononetin (3a) (15), 7-hydroxy-2-methoxyisoflavone (3b) (16) and its 2-methyl derivative 3d (17), and 7-hydroxy-2-methylisoflavone (3c), which was isolated from Glycyrrhiza glabra (18), with an equivalent amount of 2 and a two-fold excess of formalin in propan-2-ol in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP) produced derivatives of 9,10-dihydro-4H,8H-chromeno(8,7-e)(1,3)oxazin-4-one (4a-d) in satisfactory yields without preliminary preparation of N,N-bis-(hydroxymethyl)amine. Thus, we synthesized several new derivatives 4a-d containing a lupinine moiety in the 9-position as a result of simultaneous C- and O-aminomethylation of the benzopyran-4-one core. 3-Arylcoumarins, certain representatives of which were isolated from plant material, are flavonoids according to their biogenetic origin. We studied the reaction features of 3-aryl-7-hydroxycoumarins (5a-c) with 2 and formalin. Like for the 7-hydroxyisoflavones, the Mannich reaction occurred with satisfactory yield without preliminary preparation of N,N-bis-