Hassan A. El-Sayed

Synthesis and Evaluation of Antimicrobial Activity of Some Pyrimidine Glycosides

Reaction of ethyl 4-thioxo-3,4-dihydropyrimidine-5-carboxylate derivatives 1a,b and ethyl 4-oxo-3,4-dihydropyrimidine-5-carboxylate 1c with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in KOH or TEA afforded ethyl 2-aryl-4-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosylthio or/ oxy)-6-methylpyrimidine-5-carboxylate 6a-c. The glucosides 6a and 6b were obtained by the reaction of 1a and 1b with peracetylated glucose3 under MW irradiation. Mercuration of 1a followed by reaction with acetobromoglucose gave the same product 6a. The reaction of 1a-c with peracetylated ribose 4 under MW irradiation gave ethyl 2-aryl-4-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosylthio)-6-methylpyrimidine-5-carboxylate 8a–c. The deprotection of 6a–c and 8a–c in the presence of methanol and TEA/H2O afforded the deprotected products 7a–c and 9a–c. The structure were confirmed by using 1H and 13CNMR spectra. Selected members of these compounds were screened for antimicrobial activity.

Synthesis and antibacterial activity of some glucosyl- and ribosyl-pyridazin-3-ones.

Reaction of 5,6-diphenylpyridazin-3(2H)-one 1a,b with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl bromide 2 in K2CO3/acetone gave 5,6-diphenyl-N2-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl)pyridazin-3-one 5a,b. The same nucleosides 5a,b were obtained by reaction of 1a,b with peracetylated glucose 3 under MW irradiation. Mercuration of 1a,b followed by reaction with glucosyl bromide 2 gave the same nucleosides 5a,b. The riboside 4-cyano-5,6-diphenyl-N2-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)-pyridazin-3-one 8 was obtained by reaction of 4-cyanopyridazinone 1b with peracetylated ribose 7 under MW irradiation. The deprotected nucleosides 6a,b and 9 were obtained by stirring of 5a,b and 8 in methanol and TEA/H2O. The structure was confirmed using 1H and 13C-NMR spectra. Selected members of these compounds were screened for antibacterial activity.

Synthesis of Acyclovir and HBG Analogues Having Nicotinonitrile and Its 2-methyloxy 1,2,3-triazole

Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, 1H, 13C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.

Synthesis of some fused heterocyclic systems and their nucleoside candidates

A series of pyridofuro compounds were synthesized from 4-(4-chlorophenyl)-1,2-dihydro-2-oxo-6-(thiophen-2-yl)pyridine-3-carbonitrile (1) as starting material. Alkylation of 1 with ethyl bromoacetate gave the corresponding ester 2, which was condensed with hydrazine hydrate to afford the corresponding acid hydrazide derivative 3. Thrope-Ziegler cyclization of 2 with sodium methoxide gave furo[2,3-b]pyridine derivative 4, which was reacted with thiosemicarbazide, allyl isothiocyanate, formamide or hydrazine hydrate to give furopyridine derivatives 5–8, respectively. The latter compound 8 was cyclized with acetylacetone or formic acid to give the corresponding compounds 9 and 10, respectively. Furthermore, sulfurization of 1 with P2S5 gave the corresponding thioxopyridine 11, which was reacted with glycosyl (or galactosyl) bromide, morpholine or piperidine to give the corresponding thioglycoside 12a,b and Mannich base 14a,b derivatives. The deacetylation of 12a,b gave the corresponding deacetylated thioglycosides 13a,b, respectively. All the newly synthesized compounds were characterized by the elemental analyses and spectroscopic evidences (IR, 1H- and 13C NMR).

Synthesis and Antimicrobial Activity of Some 2-Pyridone Nucleosides Containing a Sulfonamide Moiety

Glycosylation of 2-pyridonesulfonamide 1a,b with glycosyl/galactosyl bromide gave the corresponding glycosides 2a,b, 3a,b, 6a,b, and 7a,b, respectively. Deacetylation of the resulting glycosides gave the corresponding glycosides 4a,b, 5a,b, 8a,b, and 9a,b, respectively, in good yields. Furthermore, reaction of 2-pyridonesulfonamide 1b with lactosyl bromide gave a mixture the corresponding N, O-lactosides 10 and 11, which were deacetylated to give the corresponding glycosides 12 and 13, respectively. The structures of the new synthesized compounds were characterized by using IR, 1H, 13C NMR spectra, and microanalysis. Selected members of these compounds were screened for antimicrobial activity.

Synthesis, Antiviral, and Antimicrobial Activity of 1,2,4-Triazole Thioglycoside Derivatives

Abstract The reaction of 5-(2-methylthio)phenyl-1,2,4-triazole-3-thiol with glucosyl, galactosyl, lactosyl bromide, and peracetylated ribose under the conventional and microwave irradiation methods afforded the corresponding S-glycosides. Deacetylation of S-glycosides gave the corresponding deacetylated derivatives. Reaction of 5-(2-methylthio)phenyl-1,2,4-triazole-3-thiol with 4-acetoxybutyl bromide, 2-acetoxyethoxymethyl bromide, 3-chloropropanol, 1,3-dichloroopropan-2-ol, epichlorohydrin, allyl bromide, and propargayl bromide gave the corresponding S-acyclonucleosides, which were deacetylated to give the corresponding deacetylated compounds. All the newly synthesized compounds were characterized by the IR, 1H, 13C NMR, and elemental analyses. Some of these compounds were screened for their antiviral and antimicrobial activity. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the related elements to view the free supplemental file. GRAPHICAL ABSTRACT

Design and synthesis of some tricyclic pyrimidines and triazines via cycloaddition and intermolecular cyclization of cyclic amidine

The cyclic amidine 3 was used as a precursor in this research, which was synthesized by chlorination of compound 1, followed by ring closure with hydrazine hydrate. Cyclization of amidine compound 3 with acetylacetone, ethyl cyanoacetate, chalcone analogue 6 and benzylidenemalononitrile (8) tolerated the expected tricyclic pyrimidines 4, 5, 7 and 9, respectively. Reaction of 3 with ammonium thiocyanate followed by cyclization of the product 10 with DMF, ethyl chloroformate and chloroacetyl chloride afforded triazine derivatives 11–13, respectively. Nucleophilic substitution of the later compound with EtONa gave ethyl methyl ether derivative 14. The benzamide derivative 15 was obtained by reaction of 3 with benzoylisothiocyanate or benzoylation of compound 10 with benzoyl chloride. Finely, heterocylization of 15 in the presence of Et3N gave the triazine derivative 16.Graphical abstract6-(4-Chlorophenyl)-4-(4-isopropylphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine (3) was used as the starting material for the synthesis of pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine and pyrido[2′,3′:3,4]pyrazolo[1,5-a][1,3,5]triazine derivatives via cycloaddition and intermolecular cyclization reactions.

An efficient and facile multicomponent synthesis of 4,6-diarylpyridine derivatives under solvent-free conditions

We present an efficient and facile synthesis of 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles (5a–j) via a four-component system of aromatic aldehydes (1), acetophenones (2), ethyl cyanoacetate (3), and ammonium acetate (4). The short reaction time coupled with the simplicity of the reaction procedure and clean reaction make this method one of the most efficient methods for synthesis of this class of compounds.

Synthesis and Anticancer Activity of Some Novel Fused Nicotinonitrile Derivatives

A series of fused nicotinonitrile derivatives was synthesized by reaction of 2,6-dioxonicotinonitrile derivative 1 with different electrophilic reagents. Reaction of pyridone 1 with benzyledine derivative 2, 3 and 7 afforded pyrano[2,3-b] pyridine 4 and 11 derivatives, respectively. Upon reaction of pyridone 1 with α,β-unsaturated carbonyl compounds and benzoyl isothiocyanate gave the corresponding pyridine derivatives 11-13 and 16, respectively, Morevere sulfurization and selenation of pyridone 1 with sulfur and selenium in the presence of triethyl amine afforded the fused pyridine 14 and 15, respectively. The structure of the new synthesized compounds was elucidated by IR, NMR and elemental analysis. Some of new synthesized pyridines were screnned for anticancer activity.

Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues

ABSTRACT Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, 1H, 13C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.