Collective synthesis of 4-Hydroxy-2-pyridone alkaloids and their antiproliferation activities

• Main Authors: Ding, Feiqing, Leow, Min Li, Ma, Jimei, William, Ronny, Liao, Hongze, Liu, Xue-Wei
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Chemistry
• Online Access: https://hdl.handle.net/10356/105307; http://hdl.handle.net/10220/20684; http://dx.doi.org/10.1002/asia.201402466
• Institution: Nanyang Technological University

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.