Synthesis of New Spirooxindole‐Fused Isoxazoline/Triazole and Isoxazoline/Isoxazole Derivatives from Three‐Component 1,3‐Dipolar Cycloaddition

Abstract

A series of diverse heterocycles containing spirooxindole, isoxazoline/triazole, and isoxazole rings has been synthesized via an efficient three‐component reaction of (E)‐2‐(1‐propargyl‐2‐oxoindoline‐3‐ylidene)acetophenones 1, arylnitrile oxides 2, and arylazides 3 using Cu(I) as catalyst. The regiochemistry and stereochemistry of cycloadducts 4a and 5a have been confirmed by X‐ray diffraction studies. The heterocycles were screened against Gram‐positive and Gram‐negative bacteria and fungi. Several compounds exhibit moderate to excellent activities comparable to those of established standard drugs.

Straightforward and Highly Diastereoselective Synthesis of a New Set of Functionalized Dispiropyrrolidines Involving Multicomponent 1,3‐Dipolar Cycloaddition with Azomethine Ylides

“…On the basis of our experimental results and previous studies on the reaction mechanism , we propose in Scheme a plausible mechanism for the regioselective and stereoselective dispiropyrrolidine formation.…”

“…This mechanism has been suggested to explain isomerization in spirooxindole alkaloids , pyrrolidines , and pyrrozilidine derivatives .…”

“…The ( Z , E ) ‐ dipole d 3 , 4 then undergoes a 1,3‐dipolar cycloaddition reaction with the dipolarophile 1 in a regioselective and stereoselective manner ( path A ). The formation of the exo‐ regioisomer 5 via path A is more favorable due to the presence of a secondary orbital interaction , which occurs between the oxygen atom of the carbonyl of the diketone and the carbon atom of the carbonyl of the dipolarophile as shown in Scheme . Conversely, the formation of the other spiroadducts 5 ′, 6 , and 6 ′ are less favorable due to steric or electronic repulsion in their corresponding transition states.…”

“…Prompted by the synthetic interest and applications of spiropyrrolidine and indanone frameworks, herein, and in continuation of our interest in azomethine ylide [3 + 2] cycloaddition reaction and in the synthesis of novel spiroheterocycles , we report the synthesis of novel series of spiro[pyrrolidine‐1‐indanone] derivatives by a one‐pot three‐component [3 + 2] cycloaddition reaction of ( E )‐2‐arylideneindanones 1 , glycine ethyl ester 2 , and the cyclic diketones isatin 3 or acenaphtenequinone 4 . Moreover, we disclose an unprecedented epimerization of spiroadducts leading to a new family of dispiropyrrolidines.…”

Indole/isatin‐containing hybrids as potential antibacterial agents

“…Hybrid 19a (MIC: 31.2 μg/ml) exhibited promising activity against Gram‐negative E. coli and P. aeruginosa , whereas 19b (MIC: 62.5 μg/ml) displayed considerable activity against Gram‐positive S. aureus and S. pyogenes , and these two hybrids were more potent than ampicillin (MIC: 100–500 μg/ml) against Gram‐negative and Gram‐positive pathogens, respectively. [ 61 ] Isatin–1,2,3‐triazole hybrids 20 and their bis‐1,2,3‐triazole analogs 21 not only possessed potential in vitro and in vivo anticancer activity (MCF‐7, HeLa, and HEK293 cell lines) but also demonstrated great potency against certain bacteria. [ 62,63 ] The SAR revealed that the introduction of the electron‐withdrawing (trifluoromethyl) group at meta ‐position of the phenyl ring and bromo group at ortho ‐position of the phenyl ring had a great influence on the antibacterial and anticancer activity.…”