A Convenient Synthesis of New Pyrazolo[4,3‐d]pyrimidines and Their Fused Heterocycles

A series of some fused heterocycles originated from pyrazolopyrimidines were synthesized using 4‐amino1‐methyl‐3‐propyl‐1H‐pyrazole‐5‐carboxamide as a starting material. The nucleophilic substitution reactions with different amino acids followed by cyclization and Suzuki–Miyaura cross‐coupling reactions with different aryl boronic acids of 7‐chloro‐5‐(4‐chlorophenyl)‐1‐methyl‐3‐propyl‐1H‐pyrazolo[4,3‐d]pyrimidine were performed. Also, the oxidative cyclization reactions of 1‐(5‐(4‐chlorophenyl)‐1‐methyl‐3‐propyl‐1H‐pyrazolo[4,3‐d]pyrimidin‐7‐yl)hydrazine with different aldehydes in the presence of diacetoxy iodobenzene are described. All the synthesized compounds were characterized by analytical and spectroscopic methods.     

A Convenient Synthesis of New Annelated Pyrimidines and Their Biological Importance

Several bicyclic/tricyclic‐fused pyrimidines were synthesized from the reactions of amino esters and bifunctional nucleophiles such as 2‐methylthio‐thiazoline and 2‐methylthio‐imidazoline. The synthesized compounds were tested for their in vitro antimicrobial activities that revealed mild to moderate growth inhibitory potentials.     

The Synthesis and Biological Evaluation of Regioisomeric Benzothiazolyl Coumarins

Various 4-aryloxymethylcoumarins have been obtained by the r.t. allylic substitution with formylphenols. These have been further reacted with o-aminothiophenol resulting in the formation of a benzothiazole skeleton. These compounds have been synthesised with a view to study their potential as microbial growth inhibitors. Comparative studies on the spectral and antimicrobial activities have also been carried out.     

A One-Pot and Convenient Synthesis of Coumarins in Solventless System

An efficient and facile preparation of simple coumarins via in situ Wittig reaction of salicylaldehydes, triphenylphosphine, and chloroethylacetate supported on MgO in satisfactory yields in solvent-free condition.     

A Convenient Synthesis of 3-Behzyl, 3-Benzyl-4-Substituted Coumarins and Their Benzo Derivatives

It is reported in the literature that alkylation of simple (unsubstituted) phosphorane with alkyl halide in ethyl acetate leads to equimolar mixture of alkylated phosphorane and salt of the unsubstituted phosphorane. Here we report exclusive formation of alkylated phosphorane from its salt from benzyl bromide in chloroform. This alkylated phosphorane (2) on reaction with 2-hydroxy carbony1 compounds (1a-1) provide E-ethyl Oc-benzyl cinnamates in high yields which on thermal cyclisation gave 3-benzylf 3-benzyl-4-substituted and benzocoumarins. Thus this method can be used conveniently to synthesise above compounds in good yields.     

Synthesis of New Fused Hetecrocyclic Compounds of Benzpyrid‐4‐One Derivatives and Their Some Biological Activity

A series of fused pyrazolino‐, Isoxazolino‐, Pyrimidino‐, Pyrimidinothino‐, thiazolidinones and β‐lactam incorporating benzpyrid‐4‐one derivatives have been synthesized by different methods of chemical reaction. The prepared compounds were established by universals and modern methods of physical and chemical confirmation.     

Synthesis and Biological Evaluation of New Fused Isoxazolo[4,5‐d] Pyridazine Derivatives

Three new heterocyclic ring systems, isoxazolo[4,5‐d]‐1,2,4‐triazolopyridazines 12‐15 , tetrazolo‐[4,3‐b]pyridazine 18 and isoxazolo[4,5‐d]pyridazino[2,3‐c]2H‐triazines 16 , 17 along with isoxazolo[4,5‐d]pyridazines 2 , 5‐10 have been synthesized. Preliminary screening of these tricyclic heterocycles revealed that some of them possess significant antibacterial and antifungal activity.     

A Convenient One‐pot Synthesis of N‐Fused 1,2,4‐Triazoles via Oxidative Cyclization Using Trichloroisocyanuric Acid

A facile one‐pot synthesis of N‐fused 1,2,4‐triazoles from heterocyclic hydrazines and aldehydes is reported. The reaction is efficiently promoted by trichloroisocyanuric acid to afford the desired products mostly in high yields and in relatively short time. The mild nature of the synthesis and short reaction time are notable advantages of the developed protocol. This protocol is effective toward various substrates having different functionalities.     

Convenient and Efficient Method for Synthesis of Bis‐Hetaryl Ketones and Evaluation of Their Antimicrobial Activity

Sodium 1‐aryl‐3‐(3‐(ethoxycarbonyl)‐5‐methyl‐1H‐pyrazol‐4‐yl)‐3‐oxoprop‐1‐en‐1‐olate was used as precursor for the preparation of some novel derivatives of various fused azolotriazine ring systems via coupling reactions with hetaryldiazonium salts. Hydrazinolysis of the latter products yielded the corresponding pyrazolopyridazine derivatives. The structures of the products were established by their spectral data and elemental analyses. The antibacterial and antifungal activities of some of the new products were also evaluated.     

Synthesis and Biological Evaluation of Bromo‐ and Fluorodanicalipin A

We disclose the syntheses of (+)‐bromodanicalipin A as well as (±)‐fluorodanicalipin A. The relative configuration and ground‐state conformation in solution of both molecules was secured by J‐based configuration analysis which revealed that these are identical to natural danicalipin A. Furthermore, preliminary toxicological investigations suggest that the adverse effect of danicalipin A may be due to the lipophilicity of the halogens.     

Green Synthesis of Fused Imidazo[1,2‐a][1,8]naphthyridine Derivatives Catalyzed by DABCO under Solvent‐Free Solid‐State Conditions and Their Biological Evaluation

An efficient and eco‐friendly methodology has been developed for the construction of fused imidazo[1,2‐a][1,8]naphthyridine derivatives in the presence of 1,4‐diazabicyclo[2.2.2]octane, and involving various substituted heterocyclic amines with phenacyl bromide under solvent‐free solid‐state condition obtained the corresponding compounds ( 5a–g , 7a–f ) in short reaction time with high yield which is the important features of this protocol. All newly synthesized products were evaluated for their antibacterial and fungal activities. All these compounds displayed good antibacterial and antifungal activity. In predominantly, compounds 7e , 7d , and 5d demonstrate the highest antibacterial and antifungal activities. Furthermore, in silico molecular docking studies results were well complemented to the antimicrobial activity.     

Solid‐phase Total Synthesis of (−)‐Apratoxin A and Its Analogues and Their Biological Evaluation

Two approaches for the solid‐phase total synthesis of apratoxin A and its derivatives were accomplished. In synthetic route A, the peptide was prepared by the sequential coupling of the corresponding amino acids on trityl chloride SynPhase Lanterns. After cleavage from the polymer‐support, macrolactamization of 10 , followed by thiazoline formation, provided apratoxin A. This approach, however, resulted in low yield because the chemoselectivity was not sufficient for the formation of the thiazoline ring though its analogue 33 was obtained. However, in synthetic route B, a cyclization precursor was prepared by solid‐phase peptide synthesis by using amino acids 13 – 15 and 18 . The final macrolactamization was performed in solution to provide apratoxin A in high overall yield. This method was then successfully applied to the synthesis of apratoxin analogues. The cytotoxic activity of the synthetic derivatives was then evaluated. The epimer 34 was as potent as apratoxin A, and O‐methyl tyrosine can be replaced by 7‐azidoheptyl tyrosine without loss of activity. The 1,3‐dipolar cycloaddition of 38 with phenylacetylene was performed in the presence of a copper catalyst without affecting the thiazoline ring.     

Convenient Synthesis of Novel Quinazoline Congeners via Copper Catalyzed C–N/C–S Coupling and Their Biological Evaluation

A library of novel quinazoline scaffolds endowed with semicarbazide/oxadiazole thiol motif synthesized via an efficient and sustainable copper catalyzed C–N/C–S coupling is reported, making the presented methodology extremely valuable from economic and environmental point of view. Among the all synthesized compounds screened for in vitro antibacterial, antifungal, and anti‐TB activity, 7b , 7c , 7f , 9b , 9c , 9i , and 9j showed excellent inhibitory effect on particular strain of bacteria, fungi, and M. tuberculosis H37Rv as well. All the newly synthesized derivatives were well characterized by their IR, ¹H NMR, ¹³C NMR, mass spectroscopy as well as elemental analysis.     

Grinding and Microwave‐assisted Synthesis of Heterocyclic Molecules in High Yields and Their Biological Evaluation

Cis‐cyclohexane1,2‐dicarboxylic acid ( 1a ), phthalic acid ( 1b ), and pyrazine 2,3‐ dicarboxylic acid ( 1c ) on grinding with hydrazine hydrate ( 2a ) gave 2‐aminohexahydro‐1H‐isoindole‐1,3(2H)‐dione ( 3a ), 2‐amino‐1H‐isoindole‐1,3(2H)‐dione ( 3b ), and 6‐amino‐5H‐pyrrolo[3,4‐b]pyrazine‐5,7(6H)‐dione ( 3c ), respectively. Condensation of ( 3a , 3b , 3c ) with aldehydes ( 4x , 4y , 4z ) and 2‐cyanopyridine, 4‐cyanopyridine, 2‐cyanopyrazine ( 5x , 5y , 5z ) under microwave irradiation gave corresponding azomethine ( 6ax , 6ay , 6az , 6bx , 6by , 6bz , 6cx , 6cy , 6cz ) and amidine ( 7ax , 7ay , 7az , 7bx , 7by , 7bz , 7cx , 7cy , 7cz ) derivatives, respectively. Fully characterized azomethine ( 6ax , 6ay , 6az , 6bx , 6by , 6bz , 6cx , 6cy , 6cz ) and amidine ( 7ax , 7ay , 7az , 7bx , 7by , 7bz , 7cx , 7cy , 7cz ) derivatives were screened for anti‐inflammatory and anticancer activity against five human cancer cell lines. Compound 7cx exhibited 35% anti‐inflammatory activity at a dose of 50 mg/kg p.o. whereas standard drug ibuprofen showed 39% activity at a dose of 50 mg/kg p.o. Compounds 6bz , 7cx , 7cz (breast T47D), 6bz , 6cy (lung NCI H‐522), 6bx , 7bz (colon HCT‐15), 6bz (ovary PA‐1) and 6bx , and 6cz (liver HepG‐2) exhibited good (35–41% inhibition at 10 μM c) anticancer activity. IC₅₀ values of 6bx , 6bz , 6cy , 6cz , 7bz , 7cx , and 7cz against various cancer cell lines and normal cell (COS‐1) are also reported.     

A Convenient Synthesis of 1,2,4‐ and 1,3,4‐Azadiphospholes

A new synthetic route to functionalized neutral and anionic azadiphospholes from easily accessible starting materials is described. Equimolar reaction of Na(OCP) and N‐(2,6‐dimethylphenyl)pivalimidoyl chloride 2 a cleanly affords the imidoxy‐functionalized 1,2,4‐azadiphosphole 3 a . Using Na(OCP) and imidoyl chloride in a 2:1 ratio leads to an anionic four‐membered ring Na[ 4 a ], which has been structurally characterized. During 16 h at room temperature, Na[ 4 a ] rearranges to the anionic 1,3,4‐azadiphospholide Na[ 5 a ] with release of carbon monoxide. Applying the more sterically demanding N‐(2,6‐diisopropylphenyl)pivalimidoyl chloride allows isolation of the 1,3,4‐azadiphospholide Na[ 5 b ] in good yield (>70 %). Possible mechanisms leading to the new isomeric azadiphospholides have been investigated with the aid of high‐level composite calculations.     

An Easy Access to Construct Some Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

The chemical reactivity of 4‐amino‐6‐benzyl‐3‐mercapto‐1,2,4‐triazine‐5(4H )‐one ( 1 ) towards various aliphatic or/and mono and bis aromatic carboxylic acid derivatives to give the corresponding fused heterocyclic systems, 1,3,4‐thiadiazoles 4 , 5 , 6 , which incorporating 1,2,4‐triazine nucleus was achieved. Moreover, compound 1 was subjected to react either with halo acetic acids or bromo ester to afford the respective fused nitrogen ring junction systems, thiadiazole 2 and 3 , or thiadiazine 7 . However, the tetracyclic ring system 9 was furnished through condensation reaction of isatine with triazine 1 . In addition, some of the new synthesized compounds were evaluated as an antioxidant and antitumor agents.     

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.     

Convenient Synthesis and Biological Activity of Mono and Diacyl 2,5‐Dimercapto‐1,3,4‐thiadiazole Derivatives

New derivatives of 2,5‐dimercapto‐1,3,4‐thiadiazole substituted both at one or two exocyclic sulfur atoms with a series of aroyl or ethoxycarbonyl groups were synthesized in reactions of 2,5‐dimercapto‐1,3,4‐thiadiazole salts with appropriate acid chlorides or ethyl chloroformate in mild conditions. The products were characterized by spectroscopy (¹H NMR, ¹³C NMR, IR, and HRMS). Some from the synthesized compounds were screened in vitro and in vivo for antibacterial and antifungal activities against a panel of reference strains of microorganisms. The study revealed that ethyl S‐(5‐mercapto‐1,3,4‐thiadiazol‐2‐yl) carbonothioate seems to be the most active and versatile compound against Gram‐positive bacteria, Gram‐negative bacteria, and plant pathogenic fungi.     

A Convenient Synthesis of 2H‐Pyran‐2‐ones,Fused Pyran‐2‐ones,and Pyridones Bearing a Thiazole Moiety

The versatile enaminonitrile, 2‐cyano‐3‐(dimethylamino)‐N‐(4‐phenylthiazol‐2‐yl)‐acrylamide ( 2 ), reacts with some C,O‐binucleophiles (acetylacetone and dimedone) in refluxing acetic acid to afford the pyranone 4 , the chromene 6 derivatives, and with C,N‐binucleophiles (2‐(benzothiazol‐2‐yl)acetonitrile and 2‐(1H‐benzimidazol‐2‐yl)acetonitrile) to afford the respective 1H‐pyrido[2,1‐b]benzothiazole 8 and pyrido[1,2‐a]benzimidazole 10 derivatives. Similar treatment of 2 with phenol, resorcinol, α‐naphthol and β‐naphthol in boiling acetic acid gave the coumarin derivatives 12 , 14 , 16 , and 18 , respectively. The utility of enaminonitrile 2 for the synthesis of 6H‐pyrano[3,2‐d]isoxazole 20 , pyrano[2,3‐c]pyrazole 22 , and pyrano[2,3‐d]pyrimidine 24 derivatives was also explored via its reaction with 3‐phenylisoxazol‐5(4H)‐one, 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one, and barbituric acid, respectively. The mechanistic aspects for the formation of the new compounds were also discussed.