Chan, Wing ChiHaynes, Richard K.Wai Chan, Dennis HoLee, Kin WoTin, Wing Shan2018-05-092018-05-092018Chan, W.C. et al. 2018. Evaluation and optimization of synthetic routes from dihydroartemisinin to the alkylamino-artemisinins artemiside and artemisone: a test of N-glycosylation methodologies on a lipophilic peroxide. Tetrahedron, 74(38):5156-5171. [https://doi.org/10.1016/j.tet.2018.04.027]0040-4020http://hdl.handle.net/10394/26849https://doi.org/10.1016/j.tet.2018.04.027https://www.sciencedirect.com/science/article/pii/S004040201830406X10-Alkylamino-artemisinins including artemiside and artemisone display enhanced activities against malaria. Earlier, dihydroartemisinin (DHA) TMS ether was converted by trimethylsilyl bromide into the 10-β-bromide that with amine nucleophiles provided the amino-artemisinins. In an attempt to develop more economic approaches, direct N-glycosylation of DHA was examined but 2-deoxyartemisinin was invariably obtained. However, hydroxyl group activation by conversion into the 10β-halide in non-polar solvents with anhydrous HCl and Group I and II metal halides, oxalyl chloride or thionyl chloride with catalytic DMSO, and oxalyl bromide did succeed. The β-halides were converted in situ by thiomorpholine into artemiside, and by thiomorpholine-1,1-dioxide into artemisone respectively in scalable reactions. Hydrogen peroxide-acetonitrile or the urea-hydrogen peroxide complex efficiently oxidized the sulfide artemiside to the sulfone artemisone. Overall, a generalized approach to 10-alkylamino-artemisinins is now availableenMalariaAntimalarial drugsArtemisininsN-glycosylationAmino-artemisininsArtemisoneArticle