Design and synthesis of sinomenine D-ring tetrazole-isoxazole and tetrazole-triazole derivatives via 1, 3-dipolar cycloaddition reaction

The synthesis of D-ring tetrazole-isoxazole and tetrazole-triazole sinomenine derivatives at N-CH3 via 1, 3-dipolar cycloaddition reactions were accomplished and a total of 34 novel sinomenine N-heterocyclic derivatives were obtained in 69-93% yields. The N-CH3 of sinomenine was first transformed into N-CN structure under the action of cyanogen bromide, and then N-CN reacted with sodium azide to give the N-tetrazole derivative. The N-H bond on tetrazole was replaced by different isoxazole bromides to get tetrazole-isoxazole sinomenine derivatives directly. The N-H bond on tetrazole was replaced by prop-argyl bromide to give sinomenine derivative with propargyl group, the terminal alkyne then reacted with the 1, 3-dipole in situ to obtain D-ring tetrazole-triazole sinomenine derivatives. All the synthesized derivatives are characterized by FT-IR, HRMS, 1H NMR, and 13C NMR spectroscopy. (c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

The synthesis of novel sinomenine N-heterocyclic derivatives, including D-ring tetrazole-isoxazole and tetrazole-triazole derivatives, was achieved through 1, 3-dipolar cycloaddition reactions at N-CH3. A total of 34 derivatives were obtained in yields of 69-93%. The N-CH3 of sinomenine was first converted into N-CN, which then reacted with sodium azide to yield the N-tetrazole derivative. Further reactions with isoxazole bromides and prop-argyl bromide resulted in the formation of tetrazole-isoxazole and tetrazole-triazole derivatives, respectively. The synthesized derivatives were characterized using FT-IR, HRMS, 1H NMR, and 13C NMR spectroscopy.