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A DBU-catalyzed inter- and intramolecular double Michael addition of donor–acceptor chromone-pyrazolone/benzofuranone synthons and 3-methyl-4-nitro-5-alkenylisoxazoles has been established, which constructed structurally diverse spiro-pyrazolone/benzofuranone-hexahydroxanthone hybrids bearing five consecutive stereocenters in good yields (up to 91%) with high diastereoselectivities (up to >20:1 dr). Moreover, this strategy further expanded the synthetic potential of bifunctional donor–acceptor chromones, and demonstrated great potential for applications in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Developed herein is a new methodology for a hybrid of two pharmacophoric oxindole and isoxazole motifs to construct isoxazole-fused 3,3′-disubstituted oxindole scaffolds via an efficient 1,6-addition reaction of 3-substituted oxindoles to 3-methyl-4-nitro-5-alkenylisoxazoles, which might generate novel drug-like molecules for biological screenings. The method gives an easy access to a series of isoxazole-fused 3,3′-disubstituted oxindoles with 26 examples in high yields (up to 92% yield) and good diastereoselectivity (up to >20:1), which makes possible the synthesis of libraries under similar circumstances. Subsequently, a sequential Michael addition/amidation/reductive cyclization process was designed for accessing this hexahydro-1H-pyrido[2,3-b]indol-2-one scaffold, which is a key structural skeleton found in a large number of biologically active natural products and pharmaceutical compounds. Hexahydro-1H-pyrido[2,3-b]indol-2-one scaffold 7cg could be obtained in 42.5% overall yield after 4 steps. [ABSTRACT FROM AUTHOR]

A diversity-oriented molecular hybridization strategy has been utilized for the synthesis of 2,3-disubstituted 1-indanol-fused 3-oxindoles through a regioselective domino Michael/Aldol reaction of 3-ylideneoxindoles 1 with malononitrile or cyanacetate ethyle 2. Products bearing consecutive stereocenters consist of an oxindole moiety and an indanol core, were smoothly obtained in high yields (up to 92% yield) with good diastereoselectivity (up to 20:1). This protocol also represents the first construction of indanol-fused 3-oxindole scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis (DOS) and the lead compound discovery. It is also worth mentioning that the reaction was completely regioselective and the competitive regioisomeric products 4 or 5 were not obtained in any case. [ABSTRACT FROM AUTHOR]

An efficient molecular hybridization strategy has been utilized for the synthesis of pirooxindole tetrahydropyranones 3 through annulation reactions of isatins 1 with 4-methylpent-3-en-2-one 2. Products consist of a pirooxindole tetrahydropyranone scaffold and propan-2-ether unit were smoothly obtained in moderate yields (up to 56% yield). The one-pot, two-step reaction, avoiding the isolation and purification of intermediates C, has proved to be a practical protocol. This protocol leads to new knowledge in the fields of both molecular complexity and the lead compound discovery. [ABSTRACT FROM AUTHOR]

A new methodology was developed for the synthesis of 3,3′-pyrrolidinyl-dispirooxindoles 3 through a 1,3-dipolar cycloaddition event of isatylidenyl-chromanones 2 with azomethine ylides (thermally generated in situ from isatins and sarcosine). The method gives an easy access to a series of highly functionalized products containing three consecutive stereocenters and vicinal spiroquaternary stereocenters fused in one ring structure with 15 examples in high yields (up to 82% yield) and good diastereoselectivity (up to >20:1), which makes possible the synthesis of libraries under similar circumstances. Moreover, the current method provides a convenient approach for the efficient incorporation of two biologically important scaffolds (chromanone and 3,3′-pyrrolidinyl-dispirooxindoles). X-ray diffraction studies of one of the cycloadducts proved the structure and regiochemistry of the cycloaddition. In particular, their biological activity against human leukemia cells K562 and normal L929 cells has been evaluated. These results suggested that 3,3′-pyrrolidinyl-dispirooxindoles 3 may be potential leads for further biological screenings. [ABSTRACT FROM AUTHOR]

Achieved herein is a novel diversity‐oriented one‐pot multicomponent synthesis of polycyclic pyrrolidinyl‐dispirooxindoles 3. The key pyrrolidine forming reaction is the 1,3‐dipolar cycloaddition event of isatylidenyl‐chromanones 2 with azomethine ylides (thermally generated in situ from isatins and proline or thioproline). Products bearing four consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure, were smoothly obtained in high yields (up to 89% yield) with good diastereoselectivity (up to >20:1). Valuable feature of this method was the design of new hybrid architectures for biological screenings through creating molecular diversity and complexity by means of the generation of several bonds and rings in a single operation. In particular, their biological activity against human leukemia cells K562 and normal L929 cells have been evaluated. These results suggested changes of this chromanone group could obviously impact the activity, and a chromanone group located in the polycyclic pyrrolidinyl‐dispirooxindoles is beneficial for the activity. What is more, the results also indicated that chromanone‐fused polycyclic pyrrolidinyl‐dispirooxindoles 3 have selective cytotoxicity against cancer cells K562 compared with normal cells L929. [ABSTRACT FROM AUTHOR]

Described herein is an environmentally benign method for the synthesis of multisubstituted 3-alkoxylated-2-oxindoles 3 via direct alkoxylation of 3-halooxindoles 1 . A wide variety of such multisubstituted 3-alkoxylated-2-oxindole scaffolds were smoothly obtained in good yields (up to 94%) by heating in an oil bath at 35 °C for 24 h. A particularly valuable feature of this method was the development of environment-friendly chemistry using alcohols 2 as both the substrates and solvents in the presence of a catalytic amount of base.

Described herein is the development of a facile and efficient methodology for the synthesis of novel turmerone motif-fused 3,3'-pyrrolidinyl-dispirooxindoles 3-5 via a multicomponent 1,3-dipolar cycloaddition of dienones 2 with azomethine ylides (thermally generated in situfrom isatins and proline or thioproline or sarcosine). Products bearing four or three consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). Another valuable application of this method was for the design of new hybrid architectures for biological screening through the adequate fusion of these sub-units of turmerone and 3,3'-pyrrolidinyl-dispirooxindole, generating drug-like molecules.