Arora Aditi, Kumar Sumit, Kumar Sandeep, Singh Sunil K, Dua Amita, Singh Brajendra K
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India.
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi, 110007, India; Department of Chemistry, Ramjas College, University of Delhi, Delhi, 110007, India.
Carbohydr Res. 2024 May;539:109105. doi: 10.1016/j.carres.2024.109105. Epub 2024 Apr 3.
Herein, we report the development of a diastereoselective and efficient route to construct sugar-derived pyrano[3,2-c]quinolones utilizing 1-C-formyl glycal and 4-hydroxy quinolone annulation. This methodology will open a route to synthesize nature inspired pyrano[3,2-c]quinolones. This is the first report for the stereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones, where 100% stereoselectivity was observed. A total of sixteen compounds have been synthesized in excellent yields with 100% stereoselectivity. The molecular docking of the synthesized novel natural product analogues demonstrated their binding modes within the active site of type II topoisomerase. The results of the in-silico studies displayed more negative binding energies for the all the synthesized compounds in comparison to the natural product huajiosimuline A, indicating their affinity for the active pocket. Ten out of the sixteen novel synthesized compounds were found to have comparative or relatively more negative binding energy in comparison to the standard anti-cancer drug, doxorubicin. Additionally, the scalability and viability of this protocol was illustrated by the gram scale synthesis.
在此，我们报道了一种利用1-C-甲酰基糖醛和4-羟基喹诺酮环化反应构建糖基吡喃并[3,2-c]喹诺酮的非对映选择性高效合成路线。该方法将为合成受天然启发的吡喃并[3,2-c]喹诺酮开辟一条途径。这是关于糖基吡喃并[3,2-c]喹诺酮立体选择性合成的首次报道，在此过程中观察到了100%的立体选择性。总共以优异的产率和100%的立体选择性合成了16种化合物。合成的新型天然产物类似物的分子对接展示了它们在II型拓扑异构酶活性位点内的结合模式。计算机模拟研究结果表明，与天然产物花椒模拟碱A相比，所有合成化合物的结合能更负，表明它们对活性口袋具有亲和力。在16种新合成的化合物中，有10种与标准抗癌药物阿霉素相比具有相当或相对更负的结合能。此外，克级规模的合成证明了该方法的可扩展性和可行性。
