Spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrid compounds were obtained in excellent yields from the regio- and stereoselective reaction between β-nitrostyrenes and non-stabilized azomethine ylides, generated in situ from isatin and phenylglycine/proline/thiaproline. These compounds were evaluated for their in vitro activity against Mycobacterium tuberculosisH37Rv (MTB). Eleven compounds were more active than pyrazinamide and one of them, namely 6′-(3-nitrophenyl)-7′-nitro-3′,6′,7′,7a′-tetrahydro-1′H-spiro-[indoline-3,5′-pyrrolo-[1,2-c]thiazol]-2-one, displayed a 7.6 μM MIC value, which represents a potency similar to that of the first-line anti-TB drug ethambutol and 6.7 times higher than that of pyrazinamide.

The L-proline-catalyzed synthesis of 7-(aryl)-8-methyl-10-phenyl-5H-benzo[h]pyrazolo-[3,4-b]quinoline-5,6(10H)-diones via the four-component sequential reaction of phenylhydrazine, 3-aminocrotononitrile, substituted benzaldehydes and 2-hydroxynaphthalene-1,4-dione is described. This “on water” protocol proceeds in high atom economy and leads to the generation of two rings, together with two C–C, one C–N and two CN bonds in a single operation. The environmental advantages of the method include short reaction time, excellent yield, easy work-up, and the absence of extraction and chromatographic purification steps.