Synthesis of novel dihydropyridine, dihydropyrimidine, dithioacetal and chalcone derivatives from formylchromones.

Condensation of 6-Formylfurochromone (4,9-dimethoxy-5-oxo-5H-furo[3,2-g][1]benzopyran-6-carbaldehyde) 5a and malononitrile without solvent afforded (2E)-2-cyano-3-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g]benzopyran-6-yl) acrylamide 8 at hydrolysis with dilute HCL. 2,6-Diamino-4-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g]benzopyran-6-yl)-1,4-dihydropyridine-3,5-dicarbonitrile 9 and 6-(2,6-diacetyl-3,5-dimethylcyclohexa-2,5-dien-1-yl)-4,9-dimethoxy-5H-furo[3,2-g][1]benzopyran-5-one 10a,b were synthesized by one-pot cyclocondensation reaction of formyl 5a, malononitrile and ammonium acetate/or ammonium hydroxide/or aniline. The reaction of formyl 5a, malononitrile/acetylacetone (Thio) urea/guanidine HCL to give 6-amino-4-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g][1]benzopyran-6-yl)-2-methylene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile compounds 11a,b, 6-(2-amino-5,6-dimethyl-1,4-dihydropyrimidin-4-yl)-4,9-dimethoxy-5H-furo[3,2-g][1]benzopyran-5-one 12a,b. Condensation of formylfurochromone 5a with thiol compounds afforded 6-isopropyl-4-methoxy-9-(methoxy Ia or methyl Ib)-5H-furo[3,2-g][1]benzopyran-5-one 13a-f; 6-(1,3-dithiolan-2-yl)-4-methoxy-5H-furo[3,2-g]chromen-5-one 14a,b; 7-hydroxy-6-isopropyl-5-methoxy-2-methyl-4H-benzopyran-4-one 5a-c; 6 hydroxy-7-[mercapto(methylthio)methyl-8-methoxy-3-methylnaphthalen-1(4H)-one 16, respectively. Formylfurochromones 5a-c were reacted with different substituted of acetyl compounds (khellinone, 2-acetyl pyrrol, 3-acetyl coumarin, methyl-2-thienyl ketone and p-aminoacetophenone respectively) to proceed 4-methoxy-9-(methoxy Ia or methyl Ib)-6-(1E)-3-oxobut-1-enyl]-5H-furo[3,2-g][1]benzopyran-5-one 17, 5-methoxy-2-methyl-6[(1E)-3-oxobut-1-enyl]-4a,5,8,8a-tetrahydro-4H-benzopyran-4-one 18a-d, 4,9-dimethoxy-6-[(1E)-3-methoxyprop-1-enyl]-5H-furo[3,2-g][1]benzopyran-5-one-N-methylene-N-phenylamine-6-(iminomethyl)-4,9-dimethoxy-5H-furo[3,2-g][1]benzopyran-5-one 19.

Synthesis and pharmaceutical activity of new series of chromonyl derivatives.

A new synthesis of chromonyl based on the reaction of formylfurochromone (4,9-dimethoxy-5-oxo-5H-furo[3,2-g][1] benzopyran-6-carbaldebyde) 1 with semicarbazide hydrochloride and thiosemicarbazide afforded 4,9-dimethoxy-5-oxo-5H-furo[3,2-gl]][1] benzopyran-6-yl-(1-aminovinyl) hydrazone derivatives 2a,b. Also 4,5-Diphenyl-2-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g][1] benzopyran-6-yl)-imidazole 3 was obtained by refluxing compound 1 with 1,2-diketone in presence of ammonium acetate. Reaction of compound 1 with different amines afforded 3-(4,9-dimethoxy-5-axo-5H-furo[3,2-g][1] benzopyran-6-yl)-aryliminoethyl derivatives 4a-g. Condensation reaction of compounds 4a-d to C-Hacid compounds were given 4-aminosubstituted-5-(6-hydroxy-4,7-dimethoxy-5-axo-5H- benzofuranyl)-pyrano[2,3-b] cyclobexa-2,3-diene 5a-d and 2-methyl-3-methoxy-4-(4-methoxypheny-lamine)-5-(6-hydroxy-4,7- dimethoxy-5-oxo-5H-benzofuranyl) 6. Refluxing compound 4d with thiosemicarbazide formed 6-methanimine-(4,9-dimethoxy-5-axo-5H-furo[3,2-g][1] benzopyran-6-yl)-(1E)-1-phenylethan-1-one thiosemicarbazide 7. Also, the reaction of compound 4d with p-aminoacetophenone gave the aryliminoethyl compound 8. The reaction of compound 4d with different aldehydes were given 3-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g][1] benzopyran)-iminomethyl-(1-aryl-1-oxo-3-proponyl substituted) 9a-d. Condensation of formyl fuorochromone 1 with phenolic compounds yielded 3-(4,9-dimethoxy-5-axo-5H-furo[3,2-g][1] benzopyran-6-yl)-derivatives 10a-d. All the tested compounds a significant increase in PT & APTT when compared with that of the control group. Only the compound IIa treated rats induced significant increase Ast, alkaline phosphatase and urea during experimental period, while other tested compounds did not cause any significant changes in liver and kidney function. Concomitantly, all the tested compound caused a significant decrease in serum cholesterol and triglyceride levels.

A new synthesis of oxadiazole, thiazolidinone, N-phthalimidoamino carbonyl and arylidene derivatives with potential antimicrobial activity.

Condensation of carbohydrazide derivatives Ia, b with dimethyl acetylenedicarboxylate and acetylenedicarboxylic acid yielded benzofuran derivatives II a-d. Reaction of Ib with aromatic aldehydes formed products III a-d. Treatment of compounds III a-d with mercaptoacetic acid yielded the cyclocondensation products (IVa-d). Phthalic anhydride reacted with compounds (Ia, b)to form products (Va, b). It has been found that both khellin and visnagin (VIa, b)react with aromatic aldehydes to give arylidene derivatives (VIIa-e). Condensation of diphenyl nitrilamine with 2-arylidene furochromones VII derivatives afforded cyclo-adducts (VIII a-i). The antibacterial activities of the selected compounds were tested against Staphylococcus aureus, B. subtilis, E. coli, Pseudomonas, Salmonella and Erwinia with good results.