Department of Process Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
Org Lett. 2020 Mar 20;22(6):2167-2172. doi: 10.1021/acs.orglett.0c00239. Epub 2020 Feb 28.
A stereoselective nine-step synthesis of the potent HIV nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir (EfdA, MK-8591) from 2-deoxyribose is described. Key findings include a diastereodivergent addition of an acetylide nucleophile to an enolizable ketone, a chemoselective ozonolysis of a terminal olefin and a biocatalytic glycosylation cascade that uses a unique strategy of byproduct precipitation to drive an otherwise-reversible transformation forward.
本文描述了从 2-脱氧核糖合成强效 HIV 核苷逆转录酶转移抑制剂（NRTTI）依发他韦（EfdA，MK-8591）的立体选择性九步合成路线。关键发现包括手性诱导的炔基亲核试剂与烯醇化酮的加成、末端烯烃的选择性臭氧化以及使用副产物沉淀的独特策略驱动的生物催化糖基化级联反应，该策略可使原本可逆的转化正向进行。
