Department of Chemistry, Seoul National University, Korea.
ACS Comb Sci. 2012 Jan 9;14(1):66-74. doi: 10.1021/co200150d. Epub 2011 Dec 1.
In this paper, we describe a regioselective synthetic pathway for enantiopure 1,3-disubstituted tetrahydroindazolone derivatives via the condensation of 2-acylcyclohexane-1,3-dione with various alkyl- and arylhydrazines using the steric effects of a Boc-protected pyrrolidine ring. This synthetic method has a broad scope for substrate generality for various hydrazines with excellent regioselectivity. To maximize the molecular diversity, further diversifications of 1,3-disubstituted tetrahydroindazolones were pursued by systematic N-modification of the secondary amine of the pyrrolidine ring using solution-phase parallel synthesis with polymer-supported reagents. A library containing a total of 272 drug-like tetrahydroindazolones, including 85 enantiomeric pairs, was constructed; the average purity, without further purification, was 95%.
在本文中，我们描述了一种通过 Boc 保护的吡咯烷环的空间位阻效应，使 2-酰基环己烷-1,3-二酮与各种烷基和芳基腙缩合，从而对映选择性地合成手性 1,3-二取代四氢吲哚酮衍生物的区域选择性合成途径。该合成方法底物通用性广泛，适用于各种腙，具有优异的区域选择性。为了最大限度地提高分子多样性，我们通过使用聚合物支持的试剂进行溶液相平行合成，对吡咯烷环的仲胺进行系统的 N 修饰，进一步对 1,3-二取代四氢吲哚酮进行多样化。构建了一个包含总共 272 种药物样四氢吲哚酮的文库，其中包括 85 对对映异构体，未经进一步纯化，其平均纯度为 95%。
