A series of isatin−dihydropyrazole hybrids have been synthesized in order to assess their potential as anticancer agents. In particular, 12 compounds were evaluated for their antiproliferative activity toward A549, IGR39, U87, MDA-MB-231, MCF-7, BT474, BxPC-3, SKOV-3, and H1299 cell lines, and human foreskin fibroblasts. Four compounds exhibited interesting antiproliferative activity and were further examined to determine their EC 50 values toward a panel of selected tumor cell lines. The best compounds were then investigated for their induced mechanism of cell death. Preliminary structure−activity relationship indicates that the presence of a substituent such as a chlorine atom or a methyl moiety in position 5 of the isatin nucleus is beneficial for the antitumor activity. EMAC4001 proved the most promising compound within the studied series with EC 50 values ranging from 0.01 to 0.38 μM.

The asymmetric synthesis of novel 3-substituted isoindolinones is herein reported. A new cascade reaction was developed that consisted of the asymmetric nitro-Mannich reaction of suitable α-amido sulfones designed from 2-formyl benzoates, followed by the in situ cyclization of the adducts. Very high enantioselectivities, up to 98% ee, and very good yields were obtained in the presence of the readily available neutral bifunctional organocatalyst derived from trans -1,2-diaminocyclohexane, which is known as Takemoto’s catalyst. The investigation of the reactivity of the obtained products allowed either the selective Boc-deprotection or reduction of the nitro group, leading to further functionalized 3-substituted isoindolinones without affecting the enantiomeric purity.

A highly stereoselective access to 3-sulfinyl-substituted isoindolinones has been achieved by a tandem organocatalytic addition/cyclization reaction of 2-carbobenzyloxy-N-tosylbenzylidenimine with thiols and succeeding diastereoselective oxidation with MCPBA. First, enantioenriched isoindolinone N,S-acetals have been obtained through a dynamic kinetic asymmetric transformation induced by a bifunctional chiral thiourea organocatalyst. In turn, the newly created carbon stereocenter enabled a high diastereocontrol in the subsequent sulfoxidation. Based on DFT calculations, a theoretical rationale for the stereoselectivity of the oxidation reaction is also provided.

An original tandem reaction consisting of a Wittig reaction−ring contraction process between α-hydroxycyclobutanone and phosphonium ylides has been developed. Highly functionalized cyclopropanecarbaldehydes are obtained in good to high yield.