title: Facile construction of structurally diverse thiazolidinedione-derived compounds via divergent stereoselective cascade organocatalysis and their biological exploratory studies.
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.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
authors.forename: Shanchao
authors.initials: S
authors.lastname: Wu
authors.forename: Shiping
authors.initials: S
authors.lastname: Zhu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003455:Cryptococcus neoformans / Q000187:drug effects; D018360:Crystallography, X-Ray; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D045162:Thiazolidinediones