Synthesis of Novel Ure Derivatives of Artemisinin ☆

The synthesis of novel artemisinin derivatives containing ure linkages 6a-c was described. 10β-azidoartemisinin (4) was first obtained in good yield by the reaction of dihydroartemisinin (2) with NaN3 in the presence of (CH3)3SiCl and a catalytic amount of KI in CH2Cl2 at ice water temperature. This compound was then hydrolyzed by Ph3P in THF/H2O at 65 oC for 6 h to furnish 10β-aminoartemisinin (5). The reaction of 5 with different isocyanates in CH2Cl2 at ambient temperature gave the target compounds 6a-c. The structures of synthesized compounds were confirmed based on spectroscopic methods: 1H and 13C NMR and comparison with published data.