一种光化学方法合成光学活性六氢-4-呋喃醇，一种高亲和力的 HIV-1 蛋白酶抑制剂 P2 配体。
A Photochemical Route to Optically Active Hexahydro-4-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors.
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. 2019 Aug 2;84(15):9801-9805. doi: 10.1021/acs.joc.9b01361. Epub 2019 Jul 16.
Abstract
We describe here the syntheses of optically pure (3a,4,7a)-hexahydro-4-furo[2,3-]pyran-4-ol and (3a,4,7a)-hexahydro-4-furo[2,3-]pyran-4-ol. These stereochemically defined heterocycles are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps involve an efficient Paternò-Büchi [2 + 2] photocycloaddition, catalytic hydrogenation, acid-catalyzed cyclization to form the racemic ligand alcohol, and an enzymatic resolution with immobilized Amano Lipase PS-30. Optically active ligands (-)- and (+)- were obtained with high enantiomeric purity. Enantiomer (-)- has been converted to potent HIV-1 protease inhibitor .
摘要
我们在这里描述了光学纯（3a,4,7a）-六氢-4-呋喃并[2,3-d]吡喃-4-醇和（3a,4,7a）-六氢-4-呋喃并[2,3-d]吡喃-4-醇的合成。这些具有明确立体化学结构的杂环是多种高效抗 HIV-1 蛋白酶抑制剂的高亲和力 P2 配体。关键步骤包括高效的 Paternò-Büchi [2 + 2]光环加成、催化氢化、酸催化环化形成外消旋配体醇，以及用固定化 Amano Lipase PS-30 进行酶拆分。得到了具有高对映体纯度的光学活性配体（-）-和（+）-。对映体（-）-已转化为有效的 HIV-1 蛋白酶抑制剂。
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