Behaviour of 4-(4-acetoaminophenyl)-4-oxobut-2-enoic acid towards carbon and nitrogen nucleophiles and use of these products in the synthesis of some interesting heterocycles

The present work is devoted to study the interaction of-aroylacrylic acid derivative (1) with some containing active methylene compounds under Michael reaction conditions and afforded the Michael adducts (2a-e). When compound 1 was allowed to react with cyclohexanone in the presence of ammonium acetate as catalyst, it afforded hydroquinoline derivative (3). Interaction of the acid 1 with highly and moderately reactive hydrocarbons e.g. p-xylene and acetanilide in the presence of anhydrous aluminumchloride under Friedel-Crafts reaction conditions afforded (4a-b). On the other hand, when the acid 1 was allowed to react with benzyl amine in dry benzene yielded 2-benzylamino-4-(4-acetaminophenyl)-4-oxobutanoic acid (5). This later compound was used to synthesize some heterocyclic compounds (7-11). Also, aza Michael adduct (6) used asthe key starting material for the synthesis of some interesting heterocyclic compounds e.g. pyridazinone, oxazinoneand furanone derivatives (13-16)

Novel synthesis, ring transformation and anticancer activity of 1,3-thiazine, pyrimidine and triazolo[1,5-a]pyrimidine derivatives

Synthesis, heterocyclization and anticancer activity of a new series of heterocyclic compounds are described. Aminothiazine 1 was obtained from the base induced condensation of thiourea, benzaldehyde and ethyl cyanoacetate. The synthesis of N-phenyl amino pyrimidine derivative 2 was obtained as a result of reaction of aniline with compound 1. Compound 2 underwent ring opening and recyclization upon reaction with HCl or H2O2/ NaOH to afford the acid derivative 3 or oxazine 4, respectively. Thiazine 1 undergoes ring transformation upon the effect of NH2OH.HCl to produce pyrimidine derivative 5. Heterocyclization of compound 1 with thiosemicarbazide followed by oxidation with I2/AcOH afforded triazolopyrimidine 6 and 7, respectively. Alkylation of compound 1 was promoted by reaction of 1 with ethyl iodide to give alkylated thiazine 8 which in turn undergo ring transformation when subjected to reaction with hydrazine hydrate to give pyrazole derivative 9. Refluxing of amino-1,3-thiazine derivative 1 with ethyl bromoacetate in the presence of Et3N produce the alkylated pyrimidine product 10. Hydrazonolysis of 1,3-thiazine 1 with hydrazine or phenyhydrazine gave pyrimidine derivatives 11a,b, respectively. Compound 11b was cyclized with carbon disulfide or formaldehyde to produce triazolopyrimidines 12 and 13, respectively. Some of the new compounds were screened for anticancer activity and significant results were found for some compounds.               KEY WORDS: 1,3-Thiazine, Pyrimidine, Triazole, Pyrazole, Anticancer activity Bull. Chem. Soc. Ethiop. 2018, 32(3), 513-522.DOI: https://dx.doi.org/10.4314/bcse.v32i3.1

Synthesis of Dynamic 2-Ethoxycarbonyl-4H-3, 1-Benzoxazin-4-one and its Behavior Towards Nitrogen Nucleophiles

The behavior of  2-ethoxycarbonyl-4H-3,1-benzoxazin-4-one and its behavior towards nitrogen nucleophiles namely, hydrazine hydrate, formamide, benzylamine, ethylamine, piperidine, ethanol amine, o-phenylenediamine, and glucosamine hydrochloride has been investigated. Also the reaction of 3-[aminoquinazolin-4(3H)-one-2-yl]formic acid hydrazide with aromatic aldehydes and phenylisothiocyanate has been discussed. The structure of the prepared compounds are elucidated using physical and spectral data like, FT-IR, 1HNMR, and mass spectroscopy

Utility of 4-(4-acetoaminophenyl)-4-oxo-but-2-enoic acid to prepare Pyranand Pyridine derivatives as building blocks in Heterocyclic Synthesis

The present work is devoted to study the interaction of β -aroylacrylic acid derivative (1) with malononitrile in the presence of piperidine and/or ammonium acetate, then using the formed compounds as a starting material for synthesizing fused and isolated heterocyclic system. Ithas been established that the β-aroylacrylic acid (1) reactwith malononitrile in (DMF) in the presence of piperidineas catalyst with formation of 4H-pyran derivative (2). Bychanging the catalyst into ammonium acetate, pyridine derivative (3) has been obtained. When compound (2) wasallowed to react with triethylorthoformate afforded ethoxymethyleneamino-4H-pyran (4). Compound (4) was used askey starting material for synthesizing some interesting annulated and heterocyclic systems (5-8). Also, the maleamic acid derivatives (9) and (15) have been synthesized via the interaction of (2) and (3) with maleic anhydride to study the behavior of the formed maleamic acid derivatives asanalogies of β-aroylacrylic towards different active methylene compounds under Michael addition reaction (10-14); (16-18)

Use of 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione in the Synthesis of Novel Quinazolinone Derivatives

The 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione 1 was synthesized and allowed to react with each of  p-methoxybenzaldehyde,  p-methoxyacetophenone and chloroacetyl chloride to produce the Schiff bases 2 and 3 and 2-chloro-N-(3-{5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1,3,4-thiadiazol-2-yl}-4-oxo-3,4-dihydroquinazolin-2-yl)acetamide 6, respectively. The products 2 and 3 were reacted with phenyl isothiocyanate to afford 4 and 5. Derivative 6 was reacted with various nucleophiles, namely: thioglycolic acid, ethyl glycinate and 2-aminoethanol giving 7-9 respectively. In turn, the derivative 8 was reacted with α-bromoglucose tetraacetate affording product 8a whereas 9 was reacted with p-acetylaminobenzenesulfonyl chloride affording derivative 9a. Moreover, the reactions of the derivative 6 with potassium thiocyanate, potassium cyanate, malonitrile, ethyl cyanoacetate and ammonium acetate gave derivatives 10-15, respectively. All the synthesized derivatives were confirmed by the IR, mass, 1H-NMR and elemental analysis. Key words: Quinazolinyl thiazolidine, thioxodiazetidinyl quinazoline, piperazinyl quinazolinone, thiomorpholine and  triazinoquinazoline

Use of 2-Ethoxy(4H)-3,1-benzoxazin-4-one as a Precursor for Synthesis of Quinazoline and Quinazolinone Starting Materials

The interactions of 2-ethoxy(4H)-3,1-benzoxazin-4-one (1) with various nitrogen nucleophiles such as ammonium acetate,  hydrazine hydrate, ethanolamine, p-phenylenediamine, o-phenylenediamine, o-tolidine, dapsone, 2-aminophenol, 4-aminophenol, 4-aminobenzoic acid and 2-aminonicotinic acid have been discussed. The reactions of 2-thoxy-(3H)-quinazolin-4-one with ethyl chloroformate, phosphorus pentasulfide, chloroacetyl chloride and phosphorus oxychloride have also been investigated. Similar reactions of 2-ethoxy-4-chloroquinazoline with hydrazine hydrate and thiosemicarbazide have been introduced. Aminolysis of the 2-ethoxy group in some of the thiadiazoloquinazolinone derivatives has been attempted. The interactions of these aminolized derivatives and the 3-aminoquinazolinone with chloroacetyl chloride have been studied. All of the synthesized derivatives have been used in a wide range as starting materials for the synthesis of novel quinazoline and/or quinazolinones which have biological activity. The structures of all these products, obtained by heterocyclic ring opening and ring closure, were inferred by the IR, MS, 1H NMR spectral as well as elemental analyses. Keywords: Aminothiadiazole, Benzoxazin-4-one, N-nucleophile, quinazoline, quinazolin-4-one, thiosemicarbazide

Protective effects of some fruit juices with low-fat diet on rat testis damaged by carbon tetrachloride: A genetic and histological study

Oxidative stress, free radical, lipid peroxidation and antioxidant have become a common expression with most disease and methods for protection. Carbon tetrachloride (CCl4) is an industrial solvent which has destructive effects on a cell while most fruit juices have antioxidant effects. The aim of this study was to investigate the protective role of fruit juice on testis after toxic effect with CCl4 through oxidative stress with basal diet and low-fat diet. Seventy-five male albino rats were used for this study in which the juices of three fresh fruit, yellow apples (Malus domestica, L.), red grapes containing seeds (Vitis vinifera, L.) and pomegranates (Punica granatum, L.) were used as therapeutic agents. Histological sections of testis indicated that low-fat diet has obvious effects than basal diet in both the low-fat diet with CCl4 "LdC""con++", LdC with grape juice 2 ml "grpL2", LdC with pomegranate juice 2 ml "pomL2" and hyper effect in LdC with pomegranate juice 4 ml "pomL4" while it was equal in effect with basal diet in the other treatments. Low-fat diet gave significant effects (about 75% recovery in con++, LdC with Apple juice 2 ml and 4 ml "appL2, appL4" , LdC with grape juice 4 ml "grpL4" and pomL2) while 25% began to recover as shown in basal diet with pomegranate juice 4 ml "pomB4" and grpL2. Treatment of rats with pomegranate juice ameliorated the toxic effects of CCl4 with low-fat diet on Semi-random RAPD-DNA profile. Low-fat diet with fruit juice had positive effect against toxicity induced by CCl4 in testes of rats on the level of histological and DNA-RAPD studies.Key words: CCl4, rat testis, yellow apples, red grapes, pomegranates, low-fat diet, oxidative stress

Progesterone utility in the synthesis of steroidal heterocyclic compounds with antitumor activity

One–pot and efficient method for the synthesis of progesteronpyridine 5a-c, 6a-c and 7a,b and/or progesteronpyran derivatives 9a-c and 10a,b by condensation reaction of progesterone 1 with different aldehydes and active methylene compounds in the presence of ammonium acetate or piperidine.  New progesteronopyrimidine derivatives 12a-d and 13a, b were synthesized via interaction of progesterone 1 with urea or thiourea and/or guanidine reagents and aldehyde. Progesterone 1 was examined to synthesize heterocyclic compound 16 containing ?-Lactone chiral carbon via the reaction of hydrazone derivative 14 with phenyl isothiocyanate followed by boiling with chloroacetic acid in benzene. The biological activity of compounds 5a, 5b, 6b, 7a, 9b, 9c, 12a, 12c, and 13a were evaluated as growth inhibitors of the liver and the breast carcinoma human cell line (HEPG2 & MCF7). Compounds 13a, 12a and 7a showed a higher potency than the standard. Key Words: Progesterone, MCR’s (multicomponents reaction), (pyridine, pyran, pyrimidine, ?-Lactone) derivatives, HEPG2 & MCF7

The mechanism of action of Spirulina as antidiabetic: a narrative review

Spirulina happens to be a special type of blue-green algae that originally emerged 3.5 billion years ago and was used as a source of nutrition. Spirulina gets its name from the filaments’ spiral or helical structure, but its true name is taxonomically Genus Arthrospira which encompasses several species. The most common species are S. fusiformis, S. maxima, and S. platensis. It is rich in various nutrients and chemical components including protein, carbohydrates, lipids, vitamins, minerals, pigments, chlorophyll, and enzymes. Spirulina’s active molecules and rich nutrients make it have several pharmacological activities and uses including antioxidant, anti-inflammatory, immunomodulatory, immune system booster, anticancer, antiviral activity, and neuroprotective properties. It is also utilized as a nutritional supplement and for weight loss. Moreover, several studies confirm that Spirulina improves insulin sensitivity and reduces blood glucose levels in rat models as well as diabetic patients. The reason behind this unique behavior could be credited to the presence of several active components in it, but the action’s fundamental mechanism is still a matter of debate. Several studies have suggested different mechanisms including anti-inflammatory activity, increased insulin sensitivity, inhibition of gluconeogenesis, antioxidant activity, modulating gut microbiota composition, improved glucose homeostasis, and insulin receptor activation. Therefore, it became clear that Spirulina is a mine of active substances used as a nutritional supplement and reduces blood glucose levels or used in conjunction with other treatments to tackle type 2 diabetes. Further exploration is required to fully explain its effects on human physiology and determine optimal dosages for treatment

MIR-99a and MIR-99b Modulate TGF-β Induced Epithelial to Mesenchymal Plasticity in Normal Murine Mammary Gland Cells

Epithelial to mesenchymal transition (EMT) is a key process during embryonic development and disease development and progression. During EMT, epithelial cells lose epithelial features and express mesenchymal cell markers, which correlate with increased cell migration and invasion. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces EMT in multiple cell types. The TGF-β pathway is regulated by microRNAs (miRNAs), which are small non-coding RNAs regulating the translation of specific messenger RNAs