Facile construction of structurally diverse thiazolidinedione-derived compounds via divergent stereoselective cascade organocatalysis and their biological exploratory studies

Yongqiang Zhang, Shengzheng Wang, Shanchao Wu, Shiping Zhu, Guoqiang Dong, Zhenyuan Miao, Jianzhong Yao, Wannian Zhang, Chunquan Sheng, Wei Wang

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

In this article, we present a new approach by merging two powerful synthetic tactics, divergent synthesis and cascade organocatalysis, to create a divergent cascade organocatalysis strategy for the facile construction of new "privileged" substructure-based DOS (pDOS) library. As demonstrated, notably 5 distinct molecular architectures are produced facilely from readily available simple synthons thiazolidinedione and its analogues and α,β-unsaturated aldehydes in 1-3 steps with the powerful strategy. The beauty of the chemistry is highlighted by the efficient formation of structurally new and diverse products from structurally close reactants under the similar reaction conditions. Notably, structurally diverse spiro-thiazolidinediones and -rhodanines are produced from organocatalytic enantioselective 3-component Michael-Michael-aldol cascade reactions of respective thiazolidinediones and rhodanines with enals. Nevertheless, under the similar reaction conditions, reactions of isorhodanine via a Michael-cyclization cascade lead to structurally different fused thiopyranoid scaffolds. This strategy significantly minimizes time- and cost-consuming synthetic works. Furthermore, these molecules possess high structural complexity and functional, stereochemical, and skeletal diversity with similarity to natural scaffolds. In the preliminary biological studies of these molecules, compounds 4f, 8a, and 10a exhibit inhibitory activity against the human breast cancer cells, while compounds 8a, 9a, and 9b display good antifungal activities against Candida albicans and Cryptococcus neoformans. Notably, their structures are different from clinically used triazole antifungal drugs. Therefore, they could serve as good lead compounds for the development of new generation of antifungal agents.

Original languageEnglish (US)
Pages (from-to)298-308
Number of pages11
JournalACS Combinatorial Science
Volume15
Issue number6
DOIs
StatePublished - Jun 10 2013
Externally publishedYes

Keywords

  • anticancer
  • antifungal
  • divergent cascade organocatalysis
  • structural diversity
  • thiazolidinedione derivatives

ASJC Scopus subject areas

  • General Chemistry

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