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The first example of bifunctional oxindole‐chromone C3 synthon directed organocatalytic cascade cycloaddition reaction is developed, serving as a fruitful strategy for the facile access of optically active tetrahydrocyclopenta[b]chromanone bearing one spirooxindole with five contiguous stereocenters. All the products are smoothly obtained with up to 83% yield, >20:1 d.r. and >99% ee. This is also the first asymmetric catalytic construction of tetrahydrocyclopenta[b] chromanone and tetrahydrocyclopenta[b]chromanone‐spirooxindole scaffold, thus to facilitate the search for new bioactive entities.magnified image

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.

A bifunctional oxindole−chromone synthon 1 directed tandem reaction is developed, serving as a fruitful strategy for facile access to optically active hexahydroxanthones 3 bearing two spirooxindoles with five contiguous stereocenters. All of the bispirooxindole-based hexahydroxanthones 3 are smoothly obtained with up to 91% yield, >20:1 dr, and >99% ee. Biological evaluation of selected compounds 3 revealed that they exerted good cytotoxic effects on human K562, A549, and PC-3 cells.S mall molecules based on privileged natural product frameworks and rich in three-dimensional complexity are in high demand in drug-discovery programs. 1 Therefore, new approaches to build novel and complex natural product-based scaffolds in an asymmetric manner remain highly desirable but challenging. 2 In this context, hexahydroxanthone bearing four or more contiguous stereocenters represents a prominent structural motif encountered in a number of natural products and pharmacologically active compounds (Figure 1). 3

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