title: Collective synthesis of 4-hydroxy-2-pyridone alkaloids and their antiproliferation activities.
abstract: A collective synthesis of 4-hydroxy-2-pyridone alkaloids--specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C--has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all-trans-polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC50 values of 7.05 μM. Hence, this approach could potentially contribute to the synthesis of bioactive small-molecule libraries as well as drug discovery.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371 (Singapore).
authors.forename: Feiqing
authors.initials: F
authors.lastname: Ding
authors.forename: Min Li
authors.initials: ML
authors.lastname: Leow
authors.forename: Jimei
authors.initials: J
authors.lastname: Ma
authors.forename: Ronny
authors.initials: R
authors.lastname: William
authors.forename: Hongze
authors.initials: H
authors.lastname: Liao
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D061986:MCF-7 Cells; D015394:Molecular Structure; D009369:Neoplasms / Q000473:pathology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011725:Pyridines; C039659:2,4-dihydroxypyridine
keywords: alkaloids; antiproliferation; cross-coupling; natural products; total synthesis