1‐Azaspiro[3.3]heptane as a Bioisostere of Piperidine**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(51)

Опубликована: Окт. 11, 2023

1-Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes the Graf isocyanate, ClO2 S-NCO, to give spirocyclic β-lactams. Reduction β-lactam ring with alane produced 1-azaspiro[3.3]heptanes. Incorporation this core into anesthetic drug bupivacaine instead piperidine fragment resulted in a new patent-free analogue high activity.

Язык: Английский

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Strain-enabled radical spirocyclization cascades: rapid access to spirocyclobutyl lactones and – lactams

Chemical Science, Год журнала: 2023, Номер 15(9), С. 3182 - 3191

Опубликована: Дек. 21, 2023

Two complementary strain-enabled radical spirocyclization cascades have been realized to synthesize spirocyclobutyl lactones and – lactams. The reactions operate under mild conditions demonstrate excellent functional group compatibility.

Язык: Английский

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Photochemical selective difluoroalkylation reactions of bicyclobutanes: direct sustainable pathways to functionalized bioisosteres for drug discovery

Green Chemistry, Год журнала: 2024, Номер 26(9), С. 5512 - 5518

Опубликована: Янв. 1, 2024

Photochemical solvent-controlled difluoromethylation and bromo-difluoromethylation reactions of bicyclobutanes are described. The method provides efficient pathways to obtain difluoroalkyl functionalized bioisosteres for drug discovery.

Язык: Английский

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Design of Inhibitors Targeting Chitin-Degrading Enzymes by Bioisostere Substitutions and Scaffold Hopping for Selective Control of Ostrinia furnacalis

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(19), С. 10794 - 10804

Опубликована: Май 7, 2024

Chitin-degrading enzymes are critical components in regulating the molting process of Asian corn borer and serve as potential targets for controlling this destructive pest maize. Here, we used a scaffold-hopping strategy to design series efficient naphthylimide insecticides. Among them, compound 8c exhibited potent inhibition chitinase from OfChi-h OfChtI at low nanomolar concentrations (IC50 = 1.51 9.21 nM, respectively). Molecular docking simulations suggested that binds by mimicking interaction chitin oligosaccharide substrates with chitinase. At ppm concentrations, performed comparably commercial insecticides highly plant pest, borer. Tests on wide range nontarget organisms indicate has very toxicity. In addition, effect inhibitor treatment expression genes associated chitin-degrading was further investigated quantitative real-time polymerase chain reaction. conclusion, our study highlights novel chitinase-targeting insecticide effective control borer, providing promising solution quest sustainable management.

Язык: Английский

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α-Amino Bicycloalkylation through Organophotoredox Catalysis

Chemical Science, Год журнала: 2024, Номер 15(28), С. 10918 - 10925

Опубликована: Янв. 1, 2024

The organophotocatalysed-generation of α-amino radicals enables the synthesis bicyclo[n.1.1]alkanes ( n = 1, 3) under mild conditions by addition to interbridgehead C–C bonds [n.1.1]propellanes.

Язык: Английский

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