Synthesis and evaluation of tetrahydroisoquinoline derivatives against Trypanosoma brucei rhodesiense

Cullen, Danica R.; Gallagher, Ashlee; Duncan, Caitlin L.; Pengon, Jutharat; Rattanajak, Roonglawan; Chaplin, Jason H.; Gunosewoyo, Hendra; Kamchonwongpaisan, Sumalee; Payne, Alan D.; Mocerino, Mauro

doi:10.1016/j.ejmech.2021.113861

Cited by 4 publications

(1 citation statement)

References 72 publications

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“…Among the developed photocatalytic transformations, the direct activation of the C–H bond has been of great interest, whereby active species can be generated via the PET pathway between the photocatalyst and C–H bonds . Herein, the direct photocatalytic oxidation of N -aryl/alkyl tetrahydroisoquinoline (THIQ), due to its critical role in organic synthesis and sensitivity to the redox reaction, − was employed to evaluate the photocatalytic performance of the TRO-COFs and TRO. Different reaction conditions were investigated to achieve the highest reaction efficiency (Table S4, entries 1–10).…”

Section: Results and Discussionmentioning

confidence: 99%

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer

Liu

et al. 2023

J. Am. Chem. Soc.

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Aryl-ketone derivatives have been acknowledged as promising organic photocatalysts for photosynthesis. However, they are limited by their photostability and have been less explored for photoinduced electron transfer (PET) applications. Herein we demonstrate a novel strategy to cover the shortage of aryl-ketone photocatalysts and control the photoreactivity by implanting symmetric aryl ketones into the conjugated covalent organic frameworks (COFs). To prove the concept, three comparative materials with the same topology and varied electronic structures were built, adopting truxenone knot and functionalized terephthalaldehyde linkers. Spectroscopic investigation and excited carrier dynamics analysis disclosed improvements in the photostability and electronic transfer efficiency as well as the structure−performance relationships toward N-aryl tetrahydroisoquinoline oxidation. This system provides a robust rule of thumb for designing new-generation aryl-ketone photocatalysts.

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Section: Results and Discussionmentioning

confidence: 99%

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer

Liu

et al. 2023

J. Am. Chem. Soc.

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Design, synthesis, and in vitro biological evaluation of novel HDAC inhibitors bearing C-1 phenyl substituted tetrahydroisoquinoline Cap moiety as anti-tumor therapeutic agents

Wang,

Zhou,

et al. 2024

Med Chem Res

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Enzyme Tunnel Dynamics and Catalytic Mechanism of Norcoclaurine Synthase: Insights from a Combined LiGaMD and DFT Study

Wang,

Liu,

Wang

et al. 2024

J. Phys. Chem. B

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This study conducts a systematic investigation into the catalytic mechanism of norcoclaurine synthase (NCS), a key enzyme in the biosynthesis of tetrahydroisoquinolines (THIQs) with therapeutic applications. By integration of LiGaMD and DFT calculations, the reaction pathway of NCS is mapped, providing detailed insights into its catalytic activity and selectivity. Our findings underscore the critical role of E103 in substrate capture and reveal the hitherto unappreciated influence of nonpolar residues M183 and L76 on tunnel dynamics. A prominent discovery is the identification of a high-energy barrier (44.2 kcal/mol) associated with the aromatic electrophilic attack, which pinpoints the rate-limiting step. Moreover, we disclose the existence of dual transition states leading to different products with the energetically favored six-membered ring formation consistent with experimental evidence. These mechanistic revelations not only refine our understanding of NCS but also advocate for a renewed emphasis on enzyme tunnel engineering for optimizing THIQs biosynthesis. The research sets the stage for translating these findings into practical enzyme modifications. Our results highlight the potential of NCS as a biocatalyst to overcome the limitations of current synthetic methodologies, such as low yields and environmental impacts, and provide a theoretical contribution to the efficient, eco-friendly production of THIQs-based pharmaceuticals.

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Synthesis and evaluation of tetrahydroisoquinoline derivatives against Trypanosoma brucei rhodesiense

Cited by 4 publications

References 72 publications

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer

Design, synthesis, and in vitro biological evaluation of novel HDAC inhibitors bearing C-1 phenyl substituted tetrahydroisoquinoline Cap moiety as anti-tumor therapeutic agents

Enzyme Tunnel Dynamics and Catalytic Mechanism of Norcoclaurine Synthase: Insights from a Combined LiGaMD and DFT Study

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