Synthesis of spiro-tetrahydrothiopyran-oxindoles by Michael–aldol cascade reactions: discovery of potential P53-MDM2 inhibitors with good antitumor activity?

Organic & Biomolecular Chemistry Pub Date: 2017-12-21 DOI: 10.1039/C7OB02726E

Abstract

Using proline as the catalyst, an organocatalytic Michael–aldol cascade reaction was developed for the synthesis of spiro-tetrahydrothiopyran oxindoles. The highly functionalized scaffold was assembled in moderate to good yields (51–78%) and excellent diastereoselectivities (>20?:?1 dr). Interestingly, the oxindoles displayed moderate to good in vitro antitumor activities and were validated as p53-MDM2 inhibitors, which represented promising lead compounds for antitumor drug discovery.

Graphical abstract: Synthesis of spiro-tetrahydrothiopyran-oxindoles by Michael–aldol cascade reactions: discovery of potential P53-MDM2 inhibitors with good antitumor activity
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