Molecular hybridization-guided one-pot multicomponent synthesis of chromanone-fused 3,3′-pyrrolidinyl-dispirooxindoles through a 1,3-dipolar cycloaddition reaction

ABSTRACT

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.

GRAPHICAL ABSTRACT

KEYWORDS:

• 1,3-Dipolar cycloaddition
• 1,3-dipolarophiles
• 3,3′-pyrrolidinyl-dispirooxindoles
• anticancer activities
• isatylidenyl-chromanones

Additional information

Funding

We are grateful for the financial support from the National Natural Science Foundations of China (No. 81660576, No. 81560563 and No. 81760625); Excellent creative talents of guizhou province (Qian Jiao He KY Zi [(2015)491] and Qian Ke He Zi [2015]4032, [2017]5609); Project of Guizhou province (Qian Ke He Zi ([2016]5623, [2015]7666 and [2015]4010) and Major project of the graduate student education teaching reform (Qian Jiao Yan He JG Zi)[2016]06.