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Diversity‐oriented Construction of Chromanone‐fused Polycyclic Pyrrolidinyl‐dispirooxindoles
Author(s) -
Feng TingTing,
Gong Yi,
Wei QiDi,
Wang GuanLian,
Liu HuanHuan,
Tian MinYi,
Liu XiongLi,
Chen ZhiYong,
Zhou Ying
Publication year - 2018
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.3145
Subject(s) - chemistry , stereocenter , pyrrolidine , oxindole , stereochemistry , k562 cells , yield (engineering) , combinatorial chemistry , in vitro , organic chemistry , enantioselective synthesis , biochemistry , materials science , metallurgy , catalysis
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.