Hatem M. Gaber

The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis

The molecular structures and spectral properties of α-haloketones as well as their syntheses are analyzed and reviewed. Their reactivity towards oxygen, nitrogen, and sulfur nucleophiles, carboxylic acids, carbon nucleophiles, alkenes, and alkynes are discussed.

Studies with functionally substituted enamines: synthesis of new aminoazolo-pyrimidines and -1,2,4-triazines

3-Aminoacrylonitrile derivatives (1d–g) coupled with aromatic and heteroaromatic diazonium salts yielding arylhydrazonals and pyrazolo[5,1-c]triazines. The enaminonitriles 1d–g condensed to form dienes 6a–c on reflux in acetic acid. The latter underwent Diels-Alder type addition to naphthoquinone. Aminopyrazolopyrimidines were obtained from reaction of 1d–g with heteroaromatic aminoazoles. Enaminonitrile 1d formed pyran 21 with benzylidene malononitrile, and dihydropyrimidine 22 with benzaldehyde and urea.

Studies on 2-Aminothiophenes: Synthesis, Transformations, and Biological Evaluation of Functionally-Substituted Thiophenes and Their Fused Derivatives

Abstract Heterocyclic enamines1 reacted with ethyl acetoacetate to afford the corresponding amide derivatives2. Treatment of2 with carbon disulphide yielded the dipotassium salts3which reacted in-situ with a variety of α -haloketones to give the respective substituted thiophenes5,8, and13. The reactivity of the latter products towards various chemical reagents was studied to yield their fused thiophene derivatives7,10,12, and14, respectively. Some representative compounds were tested for antimicrobial activity.

Studies on heterocyclic β-enaminonitriles: Synthesis of new condensed thieno[2,3-b]pyridines containing N-heterocyclic moieties

New versatile enaminonitrile-type building blocks, 3-aminothieno[2,3-b]pyridine-2-carbonitriles 3a,b, were synthesized from 3-cyanopyridine-2-(1H)-thiones 1a,b. Interaction of 3a,b with triethyl orthoformate furnished the corresponding ethoxymethylideneamino derivatives 6a,b. Derivatives of heterocyclic systems having the pyrazole, pyrimidine, and pyridine rings were obtained from the key precursors 3a,b and 6a, respectively.

β-Aminocrotononitrile in heterocyclic synthesis: Synthesis of polysubstituted pyridines as precursors to bicycles and polycycles

β-aminocrotononitrile (1) reacted with either cyanothioacetamide to give (3) or malononitrile to afford an anion (5). Pyridine-2(1H)-thione (4) was obtained by boiling of (3) in ethanol and Et 3N or treatment of (5) with H 2S, respectively. The reaction of anion 5 with isothiocyanates (6) gave N-substituted pyridine-2(1H)-thiones (7). N-Substituted pyridine-2(1H)-thiones (7) can be used for the preparation of pyrido[2,3-d]pyrimidines (8a–e) and (10a–e), or the preparation of pyrido[1,2-a]pyrimidines (12a–d). 1,8-Naphthyridine derivatives (14a–d) and (16a–e) can also be obtained from pyridine-2(1H)-thione (7). Finally, 1,8-naphthyridine derivatives (16a–e) can be used for the preparation of tetracyclic compounds 17a–c and 18a,b.

The behaviour of 4-alkoxy-methylene-2-phenyl-4H-oxazol-5-one and 4-dimethyl-amino-methylene-2-phenyl-4H-oxazol-5-one toward nitrogen nucleophiles under microwave heating

The reactivity of 4-ethoxymethylene-2-phenyloxazol-5(4H)-one and 4-dimethylamino methylene-2-phenyloxazol-5(4H)-one toward amines and active methylene reagents under microwave heating is reported. A new 3-aroylamino-4-pyridone synthesis is described.

Synthesis and antitumor activity of novel [1,2,4,5]-tetrazepino[6,7-b]indole derivatives: Marine natural productHyrtioreticuline C and D analogues

BACKGROUND Several biologically active indole alkaloids have been isolated from marine organisms over the previous few years. Many scientsts interested in synthesis of the marine azepinoindole alkaloids due to their wide range of bioliogical activies. OBJECTIVE We interested herein to synthesize a new series of some analogues of new naturally occurring azepinoindole alkaloids. METHOD A novel series of [1,2,4,5]tetrazepino[6,7-b]indoles, Marine natural product Hyrtioreticuline C and D analogues, were synthesized via the reaction of 3-hydrazonoindolin-2-one with hydrzaonoyl chlorides in basic medium. RESULTS The spectral data of the products proved their structure. All new derivatives were tested against two carcinoma cell lines ((A-549 & HepG2)) in comparison with the well-known anticancer standard drug (cisplatin) and two derivatives from the tested compounds showed activity more potent than the reference drug. CONCLUSION We succeeded in synthesis of new antitumor active azepinoindole alkaloids.

Synthesis Under Microwave Irradiation And Molecular Docking Of Some Novel Bioactive Thiadiazoles

BACKGROUND A novel series of fused imidazole was prepared from the reaction of 2- bromoacetyl-3-phenyl-1,3,4-thiadiazole with various heterocyclic amines under microwave irradiation. The structures of all the novel products were elucidated based on the elemental analysis and spectral data. RESULTS In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, analgesic and anti- ulcer agents. CONCLUSION The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.

Novel Phenylazo Derivatives of Condensed and Uncondensed Thiophene. Synthesis, Characterization, and Antimicrobial Studies

In the search for new therapeutic agents against microbial infections, two novel series of monocyclic and tricyclic 5-(phenylazo)thiophene systems were synthesized based on 3-amino-2-thioxopyrimidinone and 2-cyanoacetamidothiophene derivatives 4 and 6. Functionalization of the pyrimidine ring in precursor 4 resulted in the formation of the target tricyclic condensed thiophenes 7, 12, and 13a, b, by the application of a variety of addition, substitution, and condensation reactions. On the other hand, derivatization of the versatile cyanoacetylated compound 6 led to a second series of monocyclic N-substituted aminothiophenes 15, 17, 19, and 20, through convenient methods. The new thiophene-based derivatives were tested for their antimicrobial activity with reference to relevant standard drugs. They displayed different levels of antibacterial activity, with compound 7 showing essentially the highest antipseudomonal activity. As for antifungal action, the compounds under investigation, unfortunately, had no inhibitory effects against test fungi isolates except for 7 and 20, that revealed slight inhibition. Graphical Abstract Novel Phenylazo Derivatives of Condensed and Uncondensed Thiophene. Synthesis, Characterization, and Antimicrobial Studies