Application of a Catalytic Asymmetric Povarov Reaction using Chiral Ureas to the Synthesis of a Tetrahydroquinoline Library
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- 作者：Baudouin Gerard ; Morgan Welzel O鈥橲hea ; Etienne Donckele ; Sarathy Kesavan ; Lakshmi B. Akella ; Hao Xu ; Eric N. Jacobsen ; Lisa A. Marcaurelle
- 刊名：ACS Combinatorial Science
- 出版年：2012
- 出版时间：November 12, 2012
- 年：2012
- 卷：14
- 期：11
- 页码：621-630
- 全文大小：658K
- 年卷期：v.14,no.11(November 12, 2012)
- ISSN：2156-8944
文摘
A 2328-membered library of 2,3,4-trisubstituted tetrahydroquinolines was produced using a combination of solution- and solid-phase synthesis techniques. A tetrahydroquinoline (THQ) scaffold was prepared via an asymmetric Povarov reaction using cooperative catalysis to generate three contiguous stereogenic centers. A matrix of 4 stereoisomers of the THQ scaffold was prepared to enable the development of stereo/structure鈥揳ctivity relationships (SSAR) upon biological testing. A sparse matrix design strategy was employed to select library members to be synthesized with the goal of generating a diverse collection of tetrahydroquinolines with physicochemical properties suitable for downstream discovery.