Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218, USA.
Bioorg Med Chem Lett. 2011 May 1;21(9):2773-5. doi: 10.1016/j.bmcl.2010.09.123. Epub 2010 Sep 29.
Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally.
已经从天然三氧杂环戊烷青蒿素（1）出发，通过 4 或 5 步化学合成，制备了 4 种 5 个碳连接的三氧杂环戊烷二聚体原酸酯（6a-6d）。当使用仅 6mg/kg 体重的单一剂量，以及 18mg/kg 的盐酸甲氟喹，经口给予感染疟疾的小鼠时，三氧杂环戊烷二聚体原酸酯砜 6d 完全且安全地治愈了这些小鼠；30 天后，治愈的小鼠没有可检测到的寄生虫血症，体重增长至少与对照小鼠（无感染）相同，并且行为正常。
