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Harnessing the Substrate Promiscuity of Dioxygenase AsqJ and Developing Efficient Chemoenzymatic Synthesis for Quinolones.
Tang, Haoyu; Tang, Yijie; Kurnikov, Igor V; Liao, Hsuan-Jen; Chan, Nei-Li; Kurnikova, Maria G; Guo, Yisong; Chang, Wei-Chen.
Affiliation
  • Tang H; Department of Chemistry, North Carolina State University, Raleigh, NC.
  • Tang Y; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA.
  • Kurnikov IV; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA.
  • Liao HJ; Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taiwan.
  • Chan NL; Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taiwan.
  • Kurnikova MG; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA.
  • Guo Y; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA.
  • Chang WC; Department of Chemistry, North Carolina State University, Raleigh, NC.
ACS Catal ; 11(12): 7186-7192, 2021 Jun 18.
Article in En | MEDLINE | ID: mdl-35721870
ABSTRACT
Nature has developed complexity-generating reactions within natural product biosynthetic pathways. However, direct utilization of these pathways to prepare compound libraries remains challenging due to limited substrate scopes, involvement of multiple-step reactions, and moderate robustness of these sophisticated enzymatic transformations. Synthetic chemistry, on the other hand, offers an alternative approach to prepare natural product analogs. However, owing to complex and diverse functional groups appended on the targeted molecules, dedicated design and development of synthetic strategies are typically required. Herein, by leveraging the power of chemo-enzymatic synthesis, we report an approach to bridge the gap between biological and synthetic strategies in the preparation of quinolone alkaloid analogs. Leading by in silico analysis, the predicted substrate analogs were chemically synthesized. The AsqJ-catalyzed asymmetric epoxidation of these substrate analogues was followed by an Lewis Acid-triggered ring contraction to complete the viridicatin formation. We evaluated the robustness of this method in gram-scale reactions. Lastly, through chemoenzymatic cascades, a library of quinolone alkaloids is effectively prepared.
Key words

Full text: 1 Database: MEDLINE Language: En Journal: ACS Catal Year: 2021 Type: Article Affiliation country: New Caledonia

Full text: 1 Database: MEDLINE Language: En Journal: ACS Catal Year: 2021 Type: Article Affiliation country: New Caledonia