Bifunctional oxindole-chromone 4C building block directed asymmetric synthesis of bispirocyclic hexahydroxanthones featuring five contiguous stereocenters and two side-by-side oxindoles

Abstract

Optically active small molecules based on privileged natural product frameworks and rich in three-dimensional complexity are in high demand. In this context, the merger of two bispirooxindole and hexahydroxanthone cores is a powerful and routine strategy to develop bioactive small molecules. Here, we wish to report the bifunctional oxindole-chromone 4C building block 1 directed asymmetric synthesis of a new class of potential biological structurally bispirooxindole-based hexahydroxant-hones 3 with five adjacent stereocentres, of which two are adjacent spiro quaternary stereocentres. All the products 3 are smoothly obtained with excellent results (up to 91% yield, >20 : 1 dr and up to >99% ee). It is noteworthy that such a protocol represents a novel organocatalytic approach for the synthesis of highly desirable but challenging hexahydroxanthone derivatives, which will aid the search for new bioactive molecules.