Arteether

108739-44-2

75887-54-6

The general procedure for the synthesis of (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-ethoxy-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isobenzofuran from artemisinin (CAS: 108739-44-2) was as follows: Example 1: Artemisinin (1.0 g) was dissolved in ethanol (20 mL) with polyhydroxy catalyst dextrose (5.0 g) and stirred at room temperature for 5 minutes. Subsequently, sodium borohydride (600 mg) was slowly added over 10 min and the reaction mixture was stirred for about 1 h at room temperature (20-23°C). The progress of the reaction was monitored by thin layer chromatography (TLC) to confirm the completion of the reduction step. The acid catalyst chlorotrimethylsilane (3.5 mL) was slowly added at 10-23°C. The reaction mixture was continued to be stirred at room temperature for about 1 hour. Upon completion of the reaction, cooling water (about 150 mL) was added to the mixture and the aqueous phase was extracted with a hexane solution of 1% ethyl acetate (3 x 50 mL). The combined ethyl acetate-hexane extract was washed sequentially with 0.5% sodium bicarbonate solution (100 mL) and water (50 mL). The hexane extract was dried over anhydrous sodium sulfate and the solvent was evaporated to give 1.038 g of the crude product, which contained artemether and a few impurities. The crude product was purified by silica gel column chromatography (silica gel 10 g, eluent 0.5% to 8% ethyl acetate in hexane solution) to give a mixture of α and β arteether 0.86 g (yield 86% w/w). A small amount of arteether was taken to separate the α and β isomers by preparative thin layer chromatography (TLC) and characterized by co-thin layer chromatography (Co-TLC) and spectral analysis.