Study On Synthetic Process And Production Application Of β-artemether

As an artemisinin derivative,artemether has better parasitic clearance rate,shorter half-life and less side effects than artemisinin.It is worldly recognized as a main product among numerous antimalarial drugs.Including two epimers α-artemether andβ-artemether,the main active ingredient in artemther is β-artemether with an 6-fold antimalarial activity of artemisinin.Therefore,the industrial purification process to obtain a highly purified β-artemether product starting from a β-artemether-based mixture is of great social and economic value.Based on the published literatures,a further study was conducted on the synthesis of β-artemether.In this paper,the raw material artemether crude was first purified and then β-artemether was synthesized with an one-step process.α-Artemether in the mother liquor was recovered and transformed into β-artemether to improve the product yield.The optimized process has already been scaled up for production.During the purification of artemisinin crude,the solvent quantity,filtration and crystallization conditions were comprehensively researched in order to remove impurities from artemisinin crude and meet the pharmacopoeia specification.The method of one-step process for the synthesis of artemether was adopted after comparison between one-step process and two-step process.The catalyst,reductant,solvent,reaction temperature and other process parameters were optimized to obtain the better process conditions.The total yield from artemisinin to β-artemether is over70%,and the HPLC assay is above 99.0%.The obtained product conforms to Chinese pharmacopoeia specification.The structure is consistent with the reference substance and the potential impurities in the synthesis process have been studied as well.Finally,the mother liquor was recovered,and the α-artemether in the mother liquor was transformed into β-artemether.By optimizing the process conditions,such as vacuum distillation,extraction and reaction conditions,the obtained recovery process of β-artemether is suitable for industrial production.With this process,the conversion rate of α-artemether into β-artemether is over 40%.