奇龙方法合成(3,3,6)-六氢呋喃并[2,3-f]呋喃-3-醇，这是 HIV-1 蛋白酶抑制剂药物达芦那韦的关键亚单位。
The Chiron Approach to (3,3,6)-Hexahydrofuro[2,3-]furan-3-ol, a Key Subunit of HIV-1 Protease Inhibitor Drug, Darunavir.
机构信息
Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
出版信息
J Org Chem. 2021 Jan 1;86(1):1216-1222. doi: 10.1021/acs.joc.0c02396. Epub 2020 Dec 3.
Abstract
We describe an enantioselective synthesis of (3,3,6)-hexahydrofuro[2,3-]furan-3-ol which is a key subunit of darunavir, a widely used HIV-1 protease inhibitor drug for the treatment of HIV/AIDS patients. The synthesis was achieved in optically pure form utilizing commercially available sugar derivatives as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation, a Lewis acid catalyzed anomeric reduction of a 1,2--isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. This optically active ligand alcohol was converted to darunavir efficiently.
摘要
我们描述了（3,3,6）-六氢呋喃并[2,3-f]呋喃-3-醇的对映选择性合成，这是达鲁那韦的关键亚单位，达鲁那韦是一种广泛用于治疗 HIV/AIDS 患者的 HIV-1 蛋白酶抑制剂药物。该合成采用商业上可获得的糖衍生物作为起始原料，以光学纯形式实现。关键步骤包括高度对映选择性的底物控制氢化、路易斯酸催化的 1,2--异亚丙基保护的糖呋喃苷的端基还原以及四氢呋喃-2-醛衍生物的 Baeyer-Villiger 氧化。这种手性配体醇可有效地转化为达鲁那韦。
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