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

Abstract

The synthesis of D-ring tetrazole-isoxazole and tetrazole-triazole sinomenine derivatives at N–CH3via 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 propargyl 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.