Department of Chemistry, University of Houston , Houston, Texas 77204-5003, United States.
J Org Chem. 2016 Oct 21;81(20):9567-9575. doi: 10.1021/acs.joc.6b01476. Epub 2016 Oct 6.
The asymmetric (er > 99:1) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The Sharpless asymmetric dihydroxylation is the key asymmetric transformation used in the synthesis of this intermediate. It is carried out on an olefin that is accessed in three steps from commercially available materials, making the overall synthetic sequence very concise. The common diol intermediate derived from the Sharpless asymmetric dihydroxylation is converted into either a trans- or cis-epoxide, and these are subsequently converted to (+)-anti- and (-)-syn-mefloquine, respectively. X-ray crystallographic analysis of derivatives of (+)-anti- and (-)-syn-mefloquine is used to lay to rest a 40 year argument regarding the absolute stereochemistry of the mefloquines. A formal asymmetric (er > 99:1) synthesis of (+)-anti-mefloquine hydrochloride is also presented that uses a Sharpless asymmetric epoxidation as a key step.
描述了（+）-反式和（-）-顺式盐酸甲氟喹从一个共同中间体的不对称（er > 99:1）全合成。Sharpless 不对称双羟化反应是合成该中间体的关键不对称转化。它在烯烃上进行，该烯烃可通过三步从商业可得的材料获得，使整个合成序列非常简洁。从 Sharpless 不对称双羟化反应中得到的仲二醇中间体转化为反式或顺式环氧化物，然后分别将它们转化为（+）-反式和（-）-顺式盐酸甲氟喹。（+）-反式盐酸甲氟喹和（-）-顺式盐酸甲氟喹的衍生物的 X 射线晶体学分析用于解决关于甲氟喹的绝对立体化学的 40 年争论。还提出了一种正式的不对称（er > 99:1）（+）-反式盐酸甲氟喹的合成方法，该方法使用 Sharpless 不对称环氧化作为关键步骤。
