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Total Synthesis

Total Synthesis of Natural Products

   Natural products offer the insight into most of anticancer drugs and the development of numerous drugs having novel scaffolds. Natural product-based chemicals account for almost 60% of anticancer drugs. This implies how important it is to understand which functional group in the natural product is crucial to its activity. Goal of total synthesis of natural product is to synthesize a complex target molecule such that the product is analytically identical to the naturally occurring compound. It is not only applied in the structure investigation, but also as a test for novel synthetic methodology. This process of synthesizing complex natural products remains among the most interesting and dynamic fields of chemical research. We are in effort to conduct a total synthesis of following natural products and discover enhanced bio-active compounds by structure-activity relationship(SAR) studies.

 

   Our recent accomplishments include:

   Militarinone D

  • We synthesized Militarinone D in an efficient way compared to those previously reported methods. Our synthetic route developed for the synthesis of Militarinone D is stereo-selective and concise. This strategy may enable its utilization in the large-scale production of Militarinone D. The synthesis and biological activity screening of various new derivatives of Militarinone D are currently in progress.

   Baulamycin A

  • Total synthesis and structural revision of Baulamycin A was carried out. A comparison of the spectroscopic properties between the synthetic and natural materials demonstrated that the previously proposed stereo-structure of the natural product was incorrect. Therefore, we conducted a total synthesis of Baulamycin A and proposed the correct stereo-structure of this natural product.

Application for Derivatives of Natural Products

   Irisferin A

  • We identified the novel Reactive Oxygen Species(ROS) inducers through modification of hydrocarbon-tethered quinone moiety which is part of Irisferin A. We found them to be novel ROS inducers and reported that the naturally occurring 17-carbon chain is critical for ROS generation and selective cytotoxicity toward cancer cells, but not in noncancerous cells.

   L-783277

  • In our lab, we have discovered efficient route for making a natural product L-783277. We have also synthesized San78-130 as a derivative of L-783277 in which the alkene moiety of the cis-enone of L-783277 was saturated for ALK1 kinase activity. San78-130 is a more potent inhibitor of activin A-like kinase 1(ALK1) that it displays a better kinase selectivity against a panel of 342 kinases.