Synthesis and DNA Cleavage Activity of Novel Spiro Pyrazol-3-ones Containing Isoxazoline Moiety

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An approach to the synthesis of novel spiro pyrazol-3-ones containing isoxazoline moiety is described.A plausible mechanism for the conversion is proposed.The spiro compounds were formed via potassium carbonate-assisted intramolecular cyclocondensation reaction of β-hydroxy ketoximes, which were prepared from pyrazol-3-ones containing β-hydroxy ketone moiety through an oximation.On the other hand, treatment of the β-hydroxy ketoximes with [hydroxy(tosyloxy)iodo]benzene (HTIB) caused an oxidative N-O coupling reaction to give the spiro pyrazol-3-ones containing isoxazoline N-oxide moiety.All the synthesized compounds were characterized by spectroscopic analysis and were tested for their DNA cleavage activity.Spiro compounds, especially nitrogen-containing spiro heterocycles, served as an important structural unit in many bioactive natural products, pharmaceuticals, and agricultural chemicals. 1Among them, spiro heterocycles containing pyrazole moiety also have biological activities, such as analgesic, 2a antimicrobial, 2b antitumor, 2c and antifungal 2d activities (Figure 1).Hence, their synthesis continues to attract attention and provides an interesting challenge.On the other hand, many papers have accounted in the last decade for the synthesis and occurrence of isoxazoline derivatives in nature and medicinal chemistry. 3Besides its natural occurrence, isoxazoline is also an important skeleton found in many synthetic bioactive compounds.Isoxazoline derivatives have wide-ranging collection of conventional biological activities, for example, antimicrobial, 4 anticancer, 5 anti-inflammatory, 6 and antiplatelet 7 activities.In this context, several synthetic methods used for the formation of isoxazole and its derivatives have recently been reported in the literature. 8ompted by these observations, we focused our work on the synthesis of novel spiro pyrazol-3-ones containing isoxazoline moiety, which might have useful biological and therapeutic activities.In