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Collective Synthesis of 4‐Hydroxy‐2‐pyridone Alkaloids and Their Antiproliferation Activities
Author(s) -
Ding Feiqing,
Leow Min Li,
Ma Jimei,
William Ronny,
Liao Hongze,
Liu XueWei
Publication year - 2014
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201402466
Subject(s) - polyene , chemistry , stereochemistry , jurkat cells , combinatorial chemistry , aldol condensation , molecule , catalysis , biology , organic chemistry , t cell , immunology , immune system
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 IC 50 values of 7.05 μ M . Hence, this approach could potentially contribute to the synthesis of bioactive small‐molecule libraries as well as drug discovery.